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{{Taxobox_begin | color = violet | name = Marburg virus}}
{{Taxobox
{{Taxobox_image | image = [[Image:Marburg virus.jpg|250px|Marburg virus]] | caption = Marburg virus particles, approx. 100,000x magnification}}
<!-- Color parameter is not needed -- automatically assigned -->
{{Taxobox_begin_placement_virus}}
| name             = Marburg virus (MARV)
{{Taxobox_group_v_entry}}
| image             = Marburg virus.jpg
{{Taxobox_ordo_entry | taxon = ''[[Mononegavirales]]''}}
| image_caption    = Transmission electron micrograph of Marburg virus
{{Taxobox_familia_entry | taxon = ''[[Filoviridae]]''}}
| virus_group      = V
{{Taxobox_genus_entry | taxon = '''''Marburgvirus'''''}}
| ordo              = ''[[Mononegavirales]]''
{{Taxobox_species_entry | taxon = '''''Lake Victoria Marburgvirus'''''}}
| familia          = ''[[Filoviridae]]''
{{Taxobox_end_placement}}
| genus            = ''[[Marburgvirus]]''
{{Taxobox_end}}
| species          = ''[[Marburg marburgvirus]]''
{{Infobox_Disease |
| type_species      =
  Name          = Marburg Virus Disease |
| subdivision_ranks = Species
  Image          = |
| subdivision       =
  Caption        = |
  ICD10          = {{ICD10|A|98|3|a|90}} |
  ICD9          = {{ICD9|078.89}} |
  DiseasesDB    = 7835 |
  ICDO          = |
  OMIM          = |
  eMedicineSubj  = ped |
  eMedicineTopic = 2406 |
  MeshName       = Marburg |
  MeshNumber    = C02.782.417.560 |
}}
}}
The '''Marburg virus''' is the causative [[Biological agent|agent]] of ''' Marburg [[Viral hemorrhagic fever|hemorrhagic fever]]'''. Both the [[disease]] and [[virus]] are related to [[Ebola]] and originate in [[Uganda]] and Eastern [[Democratic Republic of the Congo|Congo]]. The [[zoonosis]] is of unknown origin, but [[fruit bat]]s are suspected.<ref>
__NOTOC__
{{cite web
{{About0|Marburg hemorrhagic fever}}
| url = http://www.msnbc.msn.com/id/20382188/
{{Marburg hemorrhagic fever}}
| title = Deadly Marburg virus discovered in fruit bats
{{CMG}}{{AE}}
| language = English
==Overview==
| accessdate = 2007-08-21
'''Marburg virus''' ({{IPAc-en|ˈ|m|ɑr|b|ər|g|_|ˈ|v|aɪ|r|ə|s}} {{Respell|MAR|bərg}} {{Respell|VY|rəs}}<ref name=KuhnArch/>) is a [[hemorrhagic fever virus]] of the Filoviridae family of viruses and a member of the species ''[[Marburg marburgvirus]]'', genus ''[[Marburgvirus]]''. Marburg virus (MARV) causes [[Marburg virus disease]] in [[human]]s and nonhuman [[primates]], a form of [[viral hemorrhagic fever]].<ref name=Spickler>{{cite web|last1=Spickler|first1=Anna|title=Ebolavirus and Marburgvirus Infections|url=http://www.cfsph.iastate.edu/Factsheets/pdfs/viral_hemorrhagic_fever_filovirus.pdf}}</ref> The virus is considered to be extremely dangerous. The [[World Health Organization|WHO]] rates it as a Risk Group 4 Pathogen (requiring [[Biosafety_level#Biosafety_level_4|biosafety level 4-equivalent containment]]).<ref name=BMBL5>{{cite web|url=http://www.cdc.gov/biosafety/publications/bmbl5/|title=Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition|accessdate=2011-10-16|last=US Department of Health and Human Services}}</ref> In the United States, the [[National Institutes of Health|NIH]]/[[National Institute of Allergy and Infectious Diseases]] ranks it as a Category A Priority Pathogen<ref name=PriorityPathogens>{{cite web|url=http://www.niaid.nih.gov/topics/biodefenserelated/biodefense/research/pages/cata.aspx |title=Biodefense and Emerging Infectious Diseases |accessdate=2011-10-16|publisher=US National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH)}}</ref> and the [[Centers for Disease Control and Prevention]] lists it as a [[Bioterrorism|Category A Bioterrorism Agent]].<ref name=CategoryBioterrorism>{{cite web|url=http://www.bt.cdc.gov/agent/agentlist-category.asp|title=Bioterrorism Agents/Diseases|accessdate=2011-10-16|last=US Centers for Disease Control and Prevention (CDC)}}</ref> It is also is listed as a biological agent for export control by the [[Australia Group]].<ref name=AustraliaGroup>{{cite web|url=http://www.australiagroup.net/en/biological_agents.html|title=List of Biological Agents for Export Control|accessdate=2011-10-16|last=The Australia Group}}</ref>
}}</ref> <!-- Green monkeys can be infected with Marburg but are not believed to be the host  -->


In the spring of [[2005]], the virus attracted widespread press attention for an outbreak in [[Angola]]. 
In 2009, expanded [[clinical trial]]s of an [[Ebola]] and Marburg [[vaccine]] began in [[Kampala]], [[Uganda]].<ref>Beth Skwarecki [http://www.medscape.com/viewarticle/831858 Ebola, Marburg DNA Vaccines Prove Safe in Phase 1 Trial] Medscape Medical News, September 17, 2014</ref><ref>[http://clinicaltrials.gov/show/NCT00997607 Evaluating an Ebola and a Marburg Vaccine in Uganda] [[U.S. Department of Health & Human Services]]</ref>
 
In September 2007 ''[[New Scientist]]'' magazine reported <ref>{{Citation | last= Mackenzie | first= Debora | publication-date= 2007-09-01 | title= Marburg virus found in fruit bats. | periodical= [[New Scientist]] | issue= 2619 | pages= p14 | url= http://www.newscientist.com/channel/health/mg19526193.200-fruit-bats-carry-deadly-marburg-virus.html | accessdate= 2007-09-26}}</ref> that the virus has been found in cave-dwelling African fruit bats in [[Gabon]], the first time the virus has been found outside humans and primates. A team in Uganda is also testing bats in a mine after two miners contracted Marburg in August 2007. [[Ebola]] genes (a close relative to Marburg) were found in three species of fruit bat in 2005. The same techniques used to identify those genes were also used to identify Marburg genes found in Egyptian fruit bats,''[[Rousettus aegyptiacus]]''. Marburg antibodies have now been found in healthy bats <ref>{{cite book | last = Towner | first = Jonathan S. | coauthors = Xavier Pourrut, César G. Albariño1, Chimène Nze Nkogue, Brian H. Bird, Gilda Girard, Thomas G. Ksiazek1, Jean-Paul Gonzalez, Stuart T. Nichol1, Eric M. Leroy | title = Marburg Virus Infection Detected in a Common African Bat | origdate = 2007-08-22 | doi = 10.1371/journal.pone.0000764}}</ref> suggesting that the bats had been previously infected. Although no-one has yet found complete live virii from a bat the team suggest that "[I] think we can be sure that these fruit bats are the reservoir of Marburg virus".
 
==The Marburg virus==
The viral structure is typical of [[filovirus]]es, with long threadlike particles which have a consistent diameter but vary greatly in length from an average of 800 [[nanometer]]s up to 14,000 nm, with peak infectious activity at about 790 nm. ''[[Virion]]s'' (viral particles) contain seven known structural [[protein]]s. While nearly identical to [[Ebola]] virus in structure, Marburg virus is [[antigen]]ically distinct from Ebola virus &mdash; in other words, it triggers different [[antibodies]] in infected organisms. It was the first [[filovirus]] to be identified. The Marburg virus was briefly described in the book written by [[Richard Preston]] entitled [[The Hot Zone]].
 
==Infection==
Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases, such as [[malaria]] or [[typhoid]], diagnosis of the disease can be difficult, especially if only a single case is involved.
 
The disease is spread through [[bodily fluid]]s, including [[blood]], [[excrement]], [[saliva]], and [[vomit]]. Early symptoms are often non-specific, and usually include fever, headache and [[myalgia]] after an incubation period of 3-9 days. After five days, a macropapular rash is often present on the trunk. Later-stage Marburg infection is acute and can include jaundice, pancreatitis, weight loss, delirium and neuropsychiatric symptoms, hemorrhaging, [[Hypovolemia|hypovolemic shock]] and multi-organ dysfunction with liver failure most common. Accounts of external [[hemorrhage|hemorrhaging]] from [[Body orifice|bodily orifices]] are pervasive in popular references to the disease but are in fact rare. Time course varies but symptoms usually last for one to three weeks until the disease either resolves or kills the infected host. The fatality rate is between 23-90% and more. <ref>
{{cite web
| url = http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm
| title = CDC special pathogins branch- Marburg page
| language =
| accessdate = 2007-05-03
}}</ref>
<ref>
{{cite web
| url = http://www.who.int/csr/don/2005_08_24/en/index.html
| title = World Health Orginization - Report after final death 2004-2005 outbreak
| language =
| accessdate = 2007-05-03
}}</ref>
   
   
If a patient survives, recovery is usually prompt and complete, though it may be prolonged in some cases. These symptoms may include inflammation or secondary infection of various organs, including: [[orchitis]] ([[testicle]]s), [[hepatitis]] ([[liver]]), [[transverse myelitis]] ([[spinal cord]]),  [[uveitis]] ([[eye]]s), or [[parotitis]] ([[parotid gland|salivary glands]]).
==Discovery==
 
Marburg virus was first described in 1967.<ref name=Siegert1967>{{cite pmid|4294540|noedit}}</ref> It was noticed during small outbreaks in the German cities [[Marburg]] and [[Frankfurt]] and the Yugoslav capital [[Belgrade]] in the 1960s. German workers were accidentally exposed to tissues of infected [[grivet|grivet monkey]]s (''Chlorocebus aethiops'') at the city's former main industrial plant, the Behringwerke, then part of [[Hoechst AG|Hoechst]], and today of [[CSL Behring]]. During these outbreaks, 31 people became infected and seven of them died. MARV is a [[Select Agent]],<ref name=SelectAgents>{{cite web|url=http://www.selectagents.gov|title=National Select Agent Registry (NSAR)|accessdate=2011-10-16|last=US Animal and Plant Health Inspection Service (APHIS) and US Centers for Disease Control and Prevention (CDC)}}</ref>  
==Treatment and prevention==
There is no specific antiviral therapy indicated for treating Marburg, and hospital care is usually supportive in nature. [[Hypotension]] and shock may require early administration of vasopressors and haemodynamic monitoring with attention to fluid and electrolyte balance, circulatory volume, and blood pressure. [[Viral hemorrhagic fever]] (VHF) patients tend to respond poorly to fluid infusions and may develop [[pulmonary edema]]. 
 
Caregivers require barrier infection control measures including double gloves, impermeable gowns, face shields, eye protection, leg and shoe coverings.
 
A few [[research]] groups are working on [[medication|drug]]s and vaccines to fight the virus. In 1998, a group at the [[United States Army Medical Research Institute of Infectious Diseases]] (USAMRIID) published the first peer reviewed article detailing the development of the first experimental Marburg virus vaccine demonstrated to completely protect animals from lethal Marburg virus infection<ref>
{{cite web
| url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9813200&query_hl=1&itool=pubmed_docsum
| title = USAMRID report on immunizations on guinea pigs that prevented infection
| language =
| accessdate = 2007-05-03
}}</ref>
Following, in [[2002]], [[Genphar]], a company doing research for the [[United States Army]]'s [[biodefense]] program, announced that an experimental vaccine protected animals from a high dose of Marburg virus. The tests were conducted by the United States Army Medical Research Institute of Infectious Diseases ([[USAMRIID]]). According to the company, all animals in the control group died within days whereas all animals that received the regular dosage of the vaccine were fully protected. The company has moved on to non-human primate trials. {{Fact|date=May 2007}} Late in [[2003]], the US government awarded the company a contract worth $8.4 million for what was described as "a multivalent Ebola, Marburg filovirus vaccine program". {{Fact|date=May 2007}}
 
In June 2005 scientists at [[Canada]]'s [[National Microbiology Laboratory]] announced that they had also developed vaccines for both Marburg and Ebola that showed significant promise in primate testing. Studies on mice also suggested that the vaccine might be an effective treatment for the disease if it is administered shortly after a patient is infected. To make the vaccines the scientists fused a surface protein from the viruses they hope to protect against onto an animal virus - [[vesicular stomatitis virus|vesicular stomatitis]] - which is thought to be of no threat to humans.<ref name="Jones2006">{{cite journal | author=Jones SM, Feldmann H, Stroher U ''et al.'' | title=Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses | journal=Nature Med | year=2005 | volume=11 | issue=7 | pages=786&ndash;90 | id=PMID 15937495 | doi=10.1038/nm1258 }}</ref>  In the rhesus macaque monkey model of the disease, the vaccine is effective even when given after infection with the virus.<ref name="Daddario-DiCaprio2006">{{cite journal | author=Daddario-DiCaprio KM,  Geisbert TW, Ströher U, ''et al.'' | title=Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment | journal=Lancet | volume=367 | issue=9520 | pages=1399&ndash;1404 | url=http://www.thelancet.com/journals/lancet/article/PIIS0140673606685462/abstract | doi=10.1016/S0140-6736(06)68546-2 }}</ref>
 
==Early outbreaks==
This virus was first documented in [[1967]], when 31 people became ill in the [[Germany|German]] town of [[Marburg]], after which it is named, as well as in [[Frankfurt am Main]] and the then [[Yugoslavia]]n city of [[Belgrade]]. The outbreak involved 25 primary infections, with 7 deaths, and 6 secondary cases, with no deaths. The primary infections were in [[laboratory]] staff exposed to the Marburg virus while working with [[monkey]]s or their tissues. The secondary cases involved two [[Physician|doctor]]s, a [[nurse]], a post-mortem attendant, and the wife of a [[veterinarian]]. All secondary cases had direct contact, usually involving blood, with a primary case. Both doctors became infected through accidental skin pricks when drawing blood from patients.


The outbreak was traced to infected African [[grivet]]s of the [[species]] ''[[Cercopithecus aethiops]]'' taken from [[Uganda]] and used in developing [[polio]] [[vaccines]]. The monkeys were imported by [[Behringwerke]], a Marburg [[company (law)|company]] founded by the first winner of the [[Nobel Prize in Medicine]], [[Emil von Behring]]. The company, which at the time was owned by [[Hoechst]], was originally set up to develop [[blood plasma|sera]] against [[tetanus]] and [[diphtheria]].
===Nomenclature===
The virus is one of two members of the [[International Committee on Taxonomy of Viruses|species]] ''[[Marburg marburgvirus]]'', which is included in the [[International Committee on Taxonomy of Viruses|genus]] ''[[Marburgvirus]]'', [[International Committee on Taxonomy of Viruses|family]] ''[[Filoviridae]]'', [[International Committee on Taxonomy of Viruses|order]] ''[[Mononegavirales]]''. The name Marburg virus is derived from [[Marburg]] (the city in [[Hesse]], [[Germany]], where the virus was first discovered) and the [[Taxonomy (biology)|taxonomic]] [[suffix]] ''virus''.<ref name=KuhnArch>{{cite pmid|21046175|noedit}}</ref>


In [[1975]], three people in the [[South African]] city of Johannesburg were infected by the Marburg virus by a man returning from [[Zimbabwe]], resulting in one death. Two similar cases in 1980 and 1987 occurred in [[Kenya]] after European visitors went to [[Kitum Cave]]. Both later died. The next major outbreak occurred in the [[Democratic Republic of Congo]] from 1998 to [[2000]], where 123 of 149 cases were fatal.  This outbreak originated with miners in Durba and Watsa in [[Orientale, Congo]].
According to the rules for taxon naming established by the [[International Committee on Taxonomy of Viruses|International Committee on Taxonomy of Viruses (ICTV)]], the name Marburg virus is always to be [[Capitalization|capitalized]], but is never [[Italic type|italicized]], and may be [[Abbreviation|abbreviated]] (with MARV being the official abbreviation).


==2004-2005 outbreak in Angola==
Marburg virus was first introduced under this name in 1967.<ref name=Siegert1967/> In 2005, the virus name was changed to Lake Victoria marburgvirus, which unfortunately was the same spelling as its species ''Lake Victoria marburgvirus''.<ref name=Feldmann2005>{{Cite book|last1=Feldmann|first1=H.|last2=Geisbert|first2=T. W.|last3=Jahrling|first3=P. B.|last4=Klenk|first4=H.-D.|last5=Netesov|first5=S. V.|last6=Peters|first6=C. J.|last7=Sanchez|first7=A.|last8=Swanepoel|first8=R.|last9=Volchkov|first9=V. E.| displayauthors = 8|chapter=Family Filoviridae|year=2005|editor-last=Fauquet|editor-first=C. M.|editor2-last=Mayo|editor2-first=M. A.|editor3-last=Maniloff|editor3-first=J.|editor4-last=Desselberger|editor4-first=U.|editor5-last=Ball|editor5-first=L. A.|title=Virus Taxonomy—Eighth Report of the International Committee on Taxonomy of Viruses|pages=645–653|publisher=Elsevier/Academic Press|location=San Diego, US|isbn=0-12-370200-3|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}</ref><ref>{{cite journal|last1=Mayo|first1=M. A.|year      = 2002|title      = ICTV at the Paris ICV: results of the plenary session and the binomial ballot|journal    = Archives of Virology|volume    = 147|issue      = 11|pages      = 2254–60|doi=10.1007/s007050200052}}</ref> However, most scientific articles continued to refer to Marburg virus. Consequently, in 2010, the name Marburg virus was reinstated and the species name changed.<ref name=KuhnArch/> A previous abbreviation for the virus was MBGV.
In early [[2005]], the [[World Health Organization]] began investigating an outbreak of a then-undiagnosed hemorrhagic fever in [[Angola]], which was centered around the northeastern [[Uige Province]]. The disease may have surfaced as early as March 2004 in a crowded children's ward. A doctor noted that a child, who subsequently died, was displaying signs of hemorrhagic fever. By October, the death rate on the ward went from three to five children a week to three to five a day. On [[March 22]], [[2005]], as the death toll neared 100, the cause of the illness was identified as the Marburg virus. By July, [[2005]], Angola's health department reported more than 300 cases were fatal. There were cases in 7 of 18 provinces but the outbreak was mostly confined to Uige province.  


According to the World Health Organization, 80% of the deaths in the early stages of the Angola outbreak were children under the age of 15, but that dropped to 30 to 40% in later stages. {{Fact|date=May 2007}} The virus has also taken a toll on health care workers, including 14 nurses and two doctors.
==Human disease==
{{Main|Marburg virus disease}}
MARV is one of two marburgviruses that causes [[Marburg virus disease|Marburg virus disease (MVD)]] in humans (in the literature also often referred to as Marburg hemorrhagic fever, MHF). Both viruses fulfill the criteria for being a member of the species Marburg marburgvirus because their [[genome]]s diverge from the prototype Marburg marburgvirus or the Marburg virus variant Musoke (MARV/Mus) by <10% at the [[nucleotide]] level.<ref name=KuhnArch/>


There has been speculation that the high death rate among children in the early stages of this outbreak may simply be due to the initial appearance of the disease in the children's ward at the Uige hospital. Early death rates (prior to effective monitoring) are meaningless as only the dead are adequately counted.
===Recorded outbreaks===
===Deaths by month===
{| class="sortable wikitable"
{| class="wikitable"
|+ [[Marburg virus disease|Marburg virus disease (MVD)]] outbreaks due to Marburg virus (MARV) infection
|+ [http://www.reliefweb.int/rw/RWB.NSF/db900SID/DDAD-6B6KXM?OpenDocument Monthly Reported Deaths]
|-
! Month year !! Deaths reported during month
|-
|-
|October 2004  || 3
| '''Year'''
|-
| '''Geographic location'''
|November 2004 || 4
| '''Human Deaths/Cases (case-fatality rate)'''
|-
|- valign="TOP"
|December 2004  || 7
| 1967
|-
| [[Marburg]] and [[Frankfurt]], West [[Germany]], and [[Belgrade]], [[Yugoslavia]]
|January 2005  || 20
| 7/31 (23%)<ref name=Siegert1967/><ref name=Smith1967>{{cite pmid|4168558|noedit}}</ref><ref name=Kissling1968>{{cite pmid|4296724|noedit}}</ref><ref name=Martini1968>{{cite pmid|4966280|noedit}}</ref><ref name=Stille1968>{{cite pmid|4966281|noedit}}</ref><ref name=Bonin1969>{{cite pmid|5005859|noedit}}</ref><ref name=Jacob1971>{{cite pmid|5748997|noedit}}</ref><ref name= Stojkovic1971>{{Cite book|last1 = Stojkovic |first1 = L.|last2 = Bordjoski |first2 = M.|last3 = Gligic |first3 = A.| last4 = Stefanovic |first4 = Z.|year = 1971|chapter = Two Cases of Cercopithecus-Monkeys-Associated Haemorrhagic Fever |editor-last=Martini|editor-first=G. A.|editor2-last=Siegert|editor2-first=R.|title=Marburg Virus Disease|pages=24–33|publisher=Springer-Verlag|location=Berlin, Germany|isbn=978-0-387-05199-4|postscript = <!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}</ref>
|-
|- valign="TOP"
|February 2005  || 30
| 1975
|-
| [[Rhodesia]] and [[Johannesburg]], [[South Africa]]
|March 2005  || 47
| 1/3 (33%)<ref name=Gear1975>{{cite pmid|811315|noedit}}</ref><ref name=Gear1977>{{cite pmid|406394|noedit}}</ref><ref name=Conrad1978>{{cite pmid|569445|noedit}}</ref>
|-
|- valign="TOP"
|April* 2005  || 123
| 1980
|-
| [[Kenya]]
|May** 2005  || 80 
| 1/2 (50%)<ref name=Smith1982>{{cite pmid|6122054|noedit}}</ref>
|- valign="TOP"
| 1987
| [[Kenya]]
| 1/1 (100%)<ref>Marburg and Ebola viruses; Advances in Virus Research;
Volume 47, 1996, Pages 1–52</ref><ref>[http://www.cdc.gov/vhf/marburg/resources/outbreak-table.html Known Cases and Outbreaks of Marburg Hemorrhagic Fever, in Chronological Order]</ref>
|- valign="TOP"
| 1988
| [[Koltsovo, Novosibirsk Oblast|Koltsovo]], [[Soviet Union]]
| 1/1 (100%) [laboratory accident]<ref name=Beer1999>{{cite pmid|10024977|noedit}}</ref>
|- valign="TOP"
| 1990
| [[Koltsovo, Novosibirsk Oblast|Koltsovo]], [[Soviet Union]]
| 0/1 (0%) [laboratory accident]<ref name=Nikiforov1994>{{cite pmid|7941853|noedit}}</ref>
|- valign="TOP"
| 1998–2000
| [[Durba, Democratic Republic of the Congo|Durba]] and [[Watsa]], [[Democratic Republic of the Congo]]
| ? (A total of 154 cases and 128 deaths of marburgvirus infection were recorded during this outbreak. The case fatality was 83%. Two different marburgviruses, MARV and [[Ravn virus|Ravn virus (RAVV)]], cocirculated and caused disease. It has never been published how many cases and deaths were due to MARV or RAVV infection)<ref name=Bertherat1999>{{cite pmid|10546197|noedit}}</ref><ref name=Bausch2003>{{cite pmid|14720391|noedit}}</ref><ref name=Bausch2006>{{cite pmid|16943403|noedit}}</ref>
|- valign="TOP"
| 2004–2005
| [[Angola]]
| 227/252 (90%)<ref name=Hovette2005>{{cite pmid|16038348|noedit}}</ref><ref name=Ndayimirije2005>{{cite pmid|15917379|noedit}}</ref><ref name=Towner2006>{{cite pmid|16775337|noedit}}</ref><ref name=Jeffs2007>{{cite pmid|17940944|noedit}}</ref><ref name=Roddy2007>{{cite pmid|17940945|noedit}}</ref><ref name=Roddy2009>{{cite pmid|18838150|noedit}}</ref><ref name=Roddy2010>{{cite pmid|20441515|noedit}}</ref>
|- valign="TOP"
| 2007
| [[Uganda]]
| 1/3 (33%)<ref name=Towner2009>{{cite pmid|19649327|noedit}}</ref><ref name=Adjemian2011>{{cite pmid|21987753|noedit}}</ref>
|- valign="TOP"
| 2008
| [[Uganda]], [[Netherlands]], [[USA]]
| 1/2 (50%)<ref name=Timen2009>{{cite pmid|19751577|noedit}}</ref>
|- valign="TOP"
| 2012
| [[Uganda]]
| 9/18 (50%)<ref>{{cite web|title=Marburg hemorrhagic fever outbreak continues in Uganda|date=October 2012|url=http://www.healio.com/pediatrics/emerging-diseases/news/online/%7B52F1CE80-ACF7-4302-AB14-05428DDDA440%7D/Marburg-hemorrhagic-fever-outbreak-continues-in-Uganda-}}</ref>
|- valign="TOP"
| 2014
| [[Uganda]]
| 1/1 (100%)<ref>{{cite web|title=1st LD-Writethru: Deadly Marburg hemorrhagic fever breaks out in Uganda|date=October 5, 2014|url=http://www.china.org.cn/world/Off_the_Wire/2014-10/05/content_33686011.htm}}</ref><ref>{{cite news |last=Ntale |first=Samson |url=http://www.cnn.com/2014/10/07/health/uganda-marburg-death/index.html?hpt=wo_bn7 |title=99 in Uganda quarantined after Marburg virus death |work=CNN |date=October 8, 2014 |accessdate=2014-10-19 }}</ref>
|}
|}
* *This represents the difference between WHO reports of April 1 and April 29..
* **This represents the difference between WHO reports of April 29 and May 27.


===Deaths by week===
==Virology==
{| class="wikitable"
|+ Weekly Reported Deaths
|-
! WHO report date !! Cumulative deaths !! Deaths during prior week
|-
|[http://www.who.int/csr/don/2005_04_01/en/index.html April 1,2005] || 132|| ''n/a''
|-
|[http://www.who.int/csr/don/2005_04_08a/en/index.html April 8, 2005]  || 180 || 48
|-
|[http://www.who.int/csr/don/2005_04_15/en/index.html April 15, 2005]*  || 207|| 27
|-
|[http://www.who.int/csr/don/2005_04_22/en/index.html April 22, 2005]  || 244|| 37
|-
|[http://www.who.int/csr/don/2005_04_29/en/index.html April 29, 2005]  || 255|| 11
|-
|[http://www.who.int/csr/don/2005_05_06/en/index.html May 6, 2005]  || 277|| 22
|-
|[http://www.who.int/csr/don/2005_05_11/en/index.html May 11, 2005]**  || 276|| -1****
|-
|[http://www.who.int/csr/don/2005_05_18/en/index.html May 18, 2005]  || 311|| 35
|-
|[http://www.who.int/csr/don/2005_05_27a/en/index.html May 27, 2005]***  || 335|| 24
|-
|[http://www.who.int/csr/don/2005_06_07/en/index.html June 7, 2005]***  || 357|| 22
|-
|[http://www.who.int/csr/don/2005_06_17/en/index.html June 17, 2005]***  || 356|| -1****
|-
|[http://www.who.int/csr/don/2005_07_13/en/index.html July 13, 2005] || 312 || *****
|}
* *No WHO report was issued [http://www.who.int/csr/don/archive/disease/marburg_virus_disease/en/ between the 15th and the 21st].  This appears associated with the [http://www.who.int/csr/don/2005_04_15/en/index.html administrative reclassification of cases].
* **Not an entire week.  No WHO report for the 13th.
* ***Over a week.
* **** No explanation provided for the decrease in cumulative deaths.
* ***** Report states that a review of data has led to a downward estimation in total deaths.


===2007 Uganda cases===
===Genome===
Marburg haemorrhagic fever (MHF) has been confirmed in a 29-year-old man in Uganda. The man became symptomatic on 4 July 2007, was admitted to hospital on 7 July and died on 14 July. The disease was confirmed by laboratory diagnosis on 30 July.
Like all [[Mononegavirales|mononegaviruses]], marburgvirions contain non-infectious, linear nonsegmented, single-stranded [[RNA]] [[genome]]s of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a [[5' cap]], are not [[Polyadenylation|polyadenylated]], and are not [[Covalent bond|covalently]] linked to a [[protein]].<ref name=Fauquet2005>{{Cite book|last1=Pringle|first1=C. R.|chapter=Order Mononegavirales|year=2005|editor-last=Fauquet|editor-first=C. M.|editor2-last=Mayo|editor2-first=M. A.|editor3-last=Maniloff|editor3-first=J.|editor4-last=Desselberger|editor4-first=U.|editor5-last=Ball|editor5-first=L. A.|title=Virus Taxonomy—Eighth Report of the International Committee on Taxonomy of Viruses|pages=609–614|publisher=Elsevier/Academic Press|location=San Diego, US|isbn=0-12-370200-3|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}</ref> Marburgvirus genomes are approximately 19 [[base pair|kb]] long and contain seven [[gene]]s in the order [[Three prime untranslated region|3'-UTR]]-''NP''-''VP35''-''VP40''-''GP''-''VP30''-''VP24''-''L''-[[Five prime untranslated region|5'-UTR]].<ref name = Kiley1982>{{cite pmid|7118520|noedit}}</ref> The genomes of the two different marburgviruses (MARV and RAVV) differ in [[nucleic acid sequence|sequence]].


The man had had prolonged close contact with a 21-year-old co-worker with a similar illness to whom he had been providing care. The 21-year-old had developed symptoms on 27 June and was hospitalized with a haemorrhagic illness. He then recovered and was discharged on 9 July. Both men were working in a mine in western Uganda.
===Structure===
[[File:Marburg em1986.png|thumb|CryoEM reconstruction of a section of the Marburg virus nucleocapsid. [[EMDB]] entry {{PDBe|EMD-1986}}<ref>{{cite PMID|22110401}}</ref>]]Like all [[Filoviridae|filoviruses]], marburgvirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched.<ref name = Kiley1982/> Marburgvirions are generally 80&nbsp;nm in [[width]], but vary somewhat in length. In general, the median particle length of marburgviruses ranges from 795 to 828&nbsp;nm (in contrast to [[Ebolavirus|ebolavirions]], whose median particle length was measured to be 974–1,086&nbsp;nm ), but particles as long as 14,000&nbsp;nm have been detected in tissue culture.<ref name = Geisbert1995>{{cite pmid|8837880|noedit}}</ref> Marburgvirions consist of seven structural proteins. At the center is the [[helical]] [[ribonucleoprotein|ribonucleocapsid]], which consists of the genomic RNA wrapped around a [[polymer]] of [[nucleoprotein]]s (NP). Associated with the ribonucleoprotein is the [[RNA-dependent RNA polymerase]] (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a [[lipid bilayer|lipid membrane]] derived from the host cell membrane. The membrane anchors a glycoprotein (GP<sub>1,2</sub>) that projects 7 to 10&nbsp;nm spikes away from its surface. While nearly identical to ebolavirions in structure, marburgvirions are [[antigen]]ically distinct.


===Control efforts===
===Entry===
Countries with direct airline links, such as [[Portugal]], screened passengers arriving from Angola. The Angolan government asked for international assistance, pointing out that there are only about 1,200 doctors in the entire country, with some provinces having as few as two. Health care workers also complained about a shortage of personal protection equipment such as gloves, gowns and masks. ''[[Médecins Sans Frontières]]'' (MSF) reported that when their team arrived at the provincial hospital at the center of the outbreak, they found it operating without [[water]] and [[electricity]]. [[Contact tracing]] is complicated by the fact that the country's roads and other infrastructure have been devastated after nearly three decades of [[Angolan War of Independence|civil war]] and the countryside remains littered with [[land mine]]s.


One innovation in the Angola outbreak has been the use of a portable laboratory operated by a team of Canadian doctors and technicians. The lab, which can operate on a [[car battery]], has eliminated the need to send blood samples outside the country for testing. This has reduced the turnaround time from days or weeks to about four hours.
[[NPC1|Niemann–Pick C1]] (NPC1) cholesterol transporter protein appears to be essential for infection with both [[Ebola virus|Ebola]] and Marburg virus. Two independent studies reported in the same issue of ''[[Nature (journal)|Nature]]'' showed that [[Ebola virus]] cell entry and replication requires NPC1.<ref name="pmid21866103">{{cite journal | author = Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR | title = Ebola virus entry requires the cholesterol transporter Niemann-Pick C1 | journal = Nature | volume = 477 | issue = 7364 | pages = 340–3 |date=September 2011 | pmid = 21866103 | pmc = 3175325 | doi = 10.1038/nature10348 | laysummary = http://www.nytimes.com/2012/01/17/health/npc1-protein-may-give-ebola-its-opening.html | laysource = New York Times }}</ref><ref name="pmid21866101">{{cite journal | author = Côté M, Misasi J, Ren T, Bruchez A, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J | title = Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection | journal = Nature | volume = 477 | issue = 7364 | pages = 344–8 |date=September 2011 | pmid = 21866101 | pmc = 3230319 | doi = 10.1038/nature10380 | laysummary = http://www.nytimes.com/2012/01/17/health/npc1-protein-may-give-ebola-its-opening.html | laysource = New York Times }}</ref> When cells from patients lacking NPC1 were exposed to Ebola virus in the laboratory, the cells survived and appeared immune to the [[virus]], further indicating that Ebola relies on NPC1 to enter cells. This might imply that genetic mutations in the NPC1 gene in humans could make some people resistant to one of the deadliest known viruses affecting humans. The same studies described similar results with Marburg virus, showing that it also needs NPC1 to enter cells.<ref name="pmid21866103"/><ref name="pmid21866101"/> Furthermore, NPC1 was shown to be critical to [[filovirus]] entry because it mediates infection by binding directly to the [[viral envelope]] glycoprotein<ref name="pmid21866101"/> and that the second lysosomal domain of NPC1 mediates this binding.<ref name="pmid22395071">{{cite journal | author = Miller EH, Obernosterer G, Raaben M, Herbert AS, Deffieu MS, Krishnan A, Ndungo E, Sandesara RG, Carette JE, Kuehne AI, Ruthel G, Pfeffer SR, Dye JM, Whelan SP, Brummelkamp TR, Chandran K | title = Ebola virus entry requires the host-programmed recognition of an intracellular receptor | journal = EMBO Journal | volume = 31 | issue = 8 | pages = 1947–60 |date=March 2012 | pmid = 22395071 | pmc = 3343336 | doi = 10.1038/emboj.2012.53 }}</ref>


Meanwhile, at [[Americo Boa Vida Hospital]] in the [[capital]], [[Luanda]], an international team prepared a special isolation ward to handle cases from the countryside. The ward was able to accommodate up to 40 patients, but there was some resistance to medical treatment. Because the disease almost invariably resulted in death, some people came to view hospitals and medical workers with suspicion and there was a brief period when medical teams were attacked in the countryside.<ref>
In one of the original studies, a [[small molecule]] was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1.<ref name="pmid21866101"/><ref name="pmid21959282">{{cite journal | author = Flemming A | title = Achilles heel of Ebola viral entry | journal = Nat Rev Drug Discov | volume = 10 | issue = 10 | pages = 731 |date=October 2011 | pmid = 21959282 | doi = 10.1038/nrd3568 }}</ref> In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse-adapted Ebola virus.<ref name="pmid21866103"/> Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola antiviral drug.
{{cite web
| url = http://www.iol.co.za/index.php?set_id=1&click_id=84&art_id=qw1113046741868B243
| title = World Health Orginization workers attacked in angola
| language =  
| accessdate = 2007-05-03
}}</ref>


A specially-equipped isolation ward at the provincial hospital in Uige was reported to be empty during much of the epidemic, even though the facility was at the center of the outbreak. WHO was forced to implement what they described as a "harm reduction strategy" which entailed distributing disinfectants to affected families who refused hospital care. An education effort and an increase in the number of Angolan health practitioners in the outbreak area, resulted in improved relations with the community. {{Fact|date=May 2007}}
===Replication===
The marburg virus [[Biological life cycle|life cycle]] begins with virion attachment to specific cell-surface [[Receptor (biochemistry)|receptors]], followed by [[Lipid bilayer fusion|fusion]] of the virion envelope with cellular membranes and the concomitant release of the virus [[nucleocapsid]] into the [[cytosol]]. The virus RdRp partially uncoats the nucleocapsid and [[Transcription (genetics)|transcribes]] the [[genes]] into positive-stranded [[mRNA]]s, which are then [[translation (biology)|translated]] into structural and nonstructural [[proteins]]. Marburgvirus L binds to a single [[Promoter (biology)|promoter]] located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the [[nucleoprotein]], whose [[concentration]] in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the [[cell membrane]]. Virions [[Budding|bud]] off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.<ref name=Feldmann2005/>


==As a weapon==
==Ecology==
The former [[Soviet Union]] reportedly had a large [[biological weapon]]s program involving Marburg. The development was conducted in [[Vector State Research Center of Virology and Biotechnology|Vector Institute]] under leadership of Dr. Ustinov who accidentally died from the virus. The samples of Marburg taken from Ustinov's organs were more powerful than the original strain. New strain called "Variant U" had been successfully weaponized and approved by Soviet Ministry of Defense in [[1990]]. <ref name="Alibek"> Alibek,K. and S. Handelman. ''Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World - Told from Inside by the Man Who Ran it.'' 1999. Delta (2000) ISBN 0-385-33496-6 </ref> United States bioterrorism grants are funding the research to develop vaccine for Marburg virus.<ref>
In 2009, the successful isolation of infectious MARV was reported from caught healthy [[Rousettus aegyptiacus|Egyptian rousettes (''Rousettus aegyptiacus'')]].<ref name="Towner2009"/> This isolation, together with the isolation of infectious [[RAVV]],<ref name=Towner2009/> strongly suggests that [[Old World]] fruit [[bat]]s are involved in the natural maintenance of marburgviruses. Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts. Recently the first experimental infection study of ''Rousettus aegyptiacus'' with MARV provided further insight into the possible involvement of these bats in MARV ecology.<ref>{{Cite journal
{{cite web
  | doi = 10.1371/journal.pone.0045479
  | url = http://www.npr.org/templates/story/story.php?storyId=4681932
| pmid = 23029039
| title = Scientists Race to Find Vaccine for Ebola, Marbug -richard knox - NPR
| title = Virological and Serological Findings in Rousettus aegyptiacus Experimentally Inoculated with Vero Cells-Adapted Hogan Strain of Marburg Virus
| language =  
| journal = PLoS ONE
| accessdate = 2007-05-03
| volume = 7
}}</ref>
| issue = 9
| pages = e45479
| year = 2012
| last1 = Paweska | first1 = J. T.
| last2 = Jansen Van Vuren | first2 = P.
| last3 = Masumu | first3 = J.
| last4 = Leman | first4 = P. A.
| last5 = Grobbelaar | first5 = A. A.
| last6 = Birkhead | first6 = M.
| last7 = Clift | first7 = S.
| last8 = Swanepoel | first8 = R.
| last9 = Kemp | first9 = A.


| pmc = 3444458
}} {{open access}}</ref> Experimentally infected bats developed relatively low viremia lasting at least 5 days, but remained healthy and didn't develop any notable gross pathology. The virus also replicated to high titers in major organs (liver and spleen), and organs that might possibly be involved in virus transmission (lung, intestine, reproductive organ, salivary gland, kidney, bladder and mammary gland). The relatively long period of viremia noted in this experiment could possibly also facilitate mechanical transmission by blood sucking arthropods or infection of susceptible vertebrate hosts by direct contact with infected blood.


==Fiction==
==Biological weapon==
In the TV series [[Millennium (TV series)|''Millennium'']], a [[prion]] version of the Marburg virus breaks out in Seattle, killing (amongst others) Frank Black's wife, Catherine.
The [[Soviet Union]] had an extensive offensive and defensive [[Biological warfare|biological weapon]]s program that included MARV.<ref name=Alibek1999>{{Cite book|last1=Alibek|first1=Steven|last2=Handelman|title=Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from Inside by the Man Who Ran It|publisher=Random House|location=New York |isbn=0-385-33496-6|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}</ref> At least three Soviet research institutes had MARV research programs during offensive times: the Virology Center of the Scientific-Research Institute for Microbiology in Zagorsk (today [[Sergiev Posad]]), the Scientific-Production Association "Vektor" (today the [[State Research Center of Virology and Biotechnology VECTOR|State Research Center of Virology and Biotechnology "Vektor"]]) in [[Koltsovo, Novosibirsk Oblast|Koltsovo]], and the Irkutsk Scientific-Research Anti-Plague Institute of Siberia and the Far East in [[Irkutsk]]. As most performed research was highly [[classified information|classified]], it remains unclear how successful the MARV program was. However, Soviet [[defection|defector]] [[Ken Alibek]] claimed that a weapon filled with MARV was tested at the [[Stepnagorsk Scientific and Technical Institute for Microbiology|Stepnogorsk Scientific Experimental and Production Base]] in [[Stepnogorsk]], [[Kazakh Soviet Socialist Republic]] (today [[Kazakhstan]]),<ref name=Alibek1999/> suggesting that the development of a MARV biological weapon had reached advanced stages. Independent confirmation for this claim is lacking. At least one laboratory accident with MARV, resulting in the death of Koltsovo researcher Nikolai Ustinov, occurred during offensive times in the Soviet Union and was first described in detail by Alibek.<ref name=Alibek1999/> After the [[dissolution of the Soviet Union]], MARV research continued in all three institutes.{{cn|date=July 2014}}


In the TV series ''[[Medical Investigation]]'', episode 17, the Marburg virus breaks out in [[New York City]], killing 5 from a total of 6 infected persons.
==In popular culture==
{{Unreferenced|section|date=June 2013}}
{{Cleanup-list|section=yes|date=October 2014}}
* In the non-fiction thriller, ''[[The Hot Zone]]'', [[Richard Preston]] describes several MARV infections.
* In the 2008 Indian science fiction movie ''[[Dasavathaaram]]'' by [[Kamal Haasan]], the plot features an intended bio weapon of "Ebola Marburg" virus.
* In the TV series [[Millennium (TV series)|''Millennium'']], at the end of Season 2, a "[[prion]] version" of MARV causes a disease outbreak in [[Seattle]], killing (amongst others) Frank Black's wife, Catherine. In the Season 3 episode "Collateral Damage", Peter Watt's daughter is infected with MARV by a Gulf War veteran who claims that the Millennium Group did the same to American soldiers during the first Gulf War.
* In the crossover event of the TV series ''[[Medical Investigation]]'', episode 17, and ''[[Third Watch]]'', season 6 episode 16, Marburg virus disease breaks out in [[New York City]], killing five of six infected people.
* In the ''[[Sarah Jane Smith]]'' series (Series Two), MARV is used as a weapon by a [[doomsday cult]].
* In the short story ''Hell Hath Enlarged Herself'' by [[Michael Marshall Smith]], one of the original scientists is infected with MARV in an attempt to test ImmunityWorks ver. 1.0.
* In the novel ''[[Microserfs]]'' by [[Douglas Coupland]], MARV is mentioned several times as a metaphor for the spread of information through the internet
* In the novel ''[[Resident Evil: Caliban Cove]]'', an insane scientist and former professor named Nicolas Griffith is referred to by Rebecca Chambers as having infected three men with MARV after they had been led to believe it was a harmless [[common cold]] virus.
* In the novel ''Pandora's Legion'' by [[Harold Coyle]] and [[Barrett Tillman]], an [[Al-Qaeda]] cell in [[Pakistan]] injects volunteers with MARV, who then board flights to major international airports in the western world where the large flow of people would facilitate the spreading of the virus into a [[pandemic]].
* In the TV series ''[[Body of Proof]]'', Season 2, episodes 18 and 19 include a MARV outbreak.
* In [[Mira Grant]]'s novel ''[[Feed (Grant novel)|Feed]]'', a modified Marburg virus that cures cancer combines with a virally transmitted cure for the common cold, resulting in a virulent viral plague that turns infected humans and animals into zombies.
* Motaba, the fictional deadly viral hemorrhagic fever, in the movie ''[[Outbreak (film)|Outbreak]]'', is based on MARV.
* In the video game ''[[Trauma Team]]'', the seventh chapter of the game, named "Patient Zero", has a storyline of a mass outbreak of the fictional Rosalia Virus, which has similar symptoms to the [[Ebola Virus]] and Marburg Virus.
* In the episode "The Order 23 Job" of the TV show ''[[Leverage (TV series)|Leverage]]'', the team's mark is led to believe that he is caught in an outbreak of weaponized Marburg virus made by the Soviets.
* In the episode "Death Is in the Air" of the TV show ''[[Psych]]'', the fictional Thornburg virus is based on the Marburg virus.
* In the episode "Small Sacrifices" of the TV show "[[House MD]]", the team explores Marburg as a diagnosis for a patient
*In the episode "The Promise" of the Canadian TV show ''[[ReGenesis]]'' Marburg was the subject of a war games exercise and a weaponized strain out of a lab in South Africa poses a potential threat.
* In the episode "Honor Among Thieves" of the TV show ''[[Person of Interest (TV series)|Person of Interest]]'', the Marburg virus is shown to be used as a potential bioterrorism agent to cause a pandemic starting in New York.
* In the episode "I Am the Apocalypse" of the TV show ''[[Chicago Fire (TV series)|Chicago Fire]]'', a man with Marburg virus attempts to start an outbreak in a Chicago hospital.
* In the TV series ''[[Bergerac (TV series)|Bergerac]]'', a potential Marburg outbreak is the subject of the episode "The Deadly Virus".


In the TV series ''[[ReGenesis]]'', episode 11, the source of an earlier Marburg outbreak is investigated.
==References==
{{Reflist|2}}


In the Sarah Jane Smith series of audios (Series Two) the virus is used as a weapon by a [[doomsday event|Doomsday cult]]. [http://doctorwho.co.uk/drwho_sarahjane/SJS203_fatal.shtml here]
==Further reading==
{{Refbegin}}
* {{Cite book|last=Klenk|first=Hans-Dieter|title=Marburg and Ebola Viruses. Current Topics in Microbiology and Immunology, vol. 235|year=1999|publisher=Springer-Verlag|location=Berlin, Germany|isbn=978-3-540-64729-4|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}
* {{Cite book|first1=Hans-Dieter|last1=Klenk|first2=Heinz|last2=Feldmann|title=Ebola and Marburg Viruses: Molecular and Cellular Biology|year=2004|publisher=Horizon Bioscience|location=Wymondham, Norfolk, UK|isbn=978-1-904933-49-6|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}
* {{Cite book|last=Kuhn|first=Jens H.|title=Filoviruses: A Compendium of 40 Years of Epidemiological, Clinical, and Laboratory Studies. Archives of Virology Supplement, vol. 20|year=2008|publisher=SpringerWienNewYork|location=Vienna, Austria|isbn=978-3-211-20670-6|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}
* {{Cite book|last1=Martini|first1=G. A.|last2=Siegert|first2=R.|title=Marburg Virus Disease|year=1971|publisher=Springer-Verlag|location=Berlin, Germany|isbn=978-0-387-05199-4}}
* {{Cite book|last1=Ryabchikova|first1=Elena I.|last2=Price|first2=Barbara B.|title=Ebola and Marburg Viruses: A View of Infection Using Electron Microscopy|year=2004|publisher=Battelle Press|location=Columbus, Ohio, US
|isbn=978-1-57477-131-2|postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}
{{Refend}}


In the novel ''Cain'' by James Byron Huggins, the being known as Cain, a genetically engineered monster, is infected with a modified form of the Marburg virus which, if released, could potentially wipe out humanity.
==External links==
 
{{Commons category|Marburg virus}}
In the short story ''Hell Hath Enlarged Herself'' by [[Michael Marshall Smith]], one of the original scientists is infected with Marburg in an attempt to test ImmunityWorks ver. 1.0.
* [http://talk.ictvonline.org International Committee on Taxonomy of Viruses (ICTV)]
 
* [http://www.filovir.com FILOVIR - scientific resources for research on filoviruses]
In the novel ''Gravity'' by [[Tess Gerritsen]], an outbreak of Marburg virus is suspected on the International Space Station.  The infectious agent turns out to be not Marburg, but rather a [[chimera (virus)|chimera virus]].
 
In the novel ''Microserfs'' by [[Douglas Coupland]], the Marburg virus is mentioned several times as a metaphor for the spread of information through the internet.
 
In the film ''WW3: Winds of Terror'' (2001), directed by Robert Mandel, a variant of Marburg becomes a deadly bioweapon that can be used by terrorists.
 
In The novel [[Resident Evil: Caliban Cove]] a mad Scientist named Nicolas Griffith is referred to by Rebecca Chambers as having infected two men with the [[Marburg virus]] after they had been led to believe it was a harmless cold virus.


==Further reading (Nonfiction)==
{{Filoviridae}}
{{commons|Marburg virus}}
* [[Ebola]]
* ''[[Biohazard (book)|Biohazard]]'', a book by [[Ken Alibek]]
* ''[[The Hot Zone]]'', a book by [[Richard Preston]] ISBN 0-517-17158-9
* ''The Coming Plague'', a book by [[Laurie Garrett]] ISBN 0-374-12646-1
* ''Plagues and Peoples'', a book by [[William McNeill]] ISBN 0-8446-6492-8
* [[Lassa fever]]


==References==
[[Category:Marburgviruses| ]]
<div class="references-2column">{{reflist|2}}</div>
[[Category:Animal virology]]
 
[[Category:Arthropod-borne viral fevers and viral haemorrhagic fevers]]
==External links==
* [[Center for Disease Control]], ''[http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual.htm Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting]''.
* Center for Disease Control, ''[http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm Marburg Haemorrhagic Fever]''.
* Center for Disease Control, ''[http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg/marburgtable.htm Known Cases and Outbreaks of Marburg Hemorrhagic Fever]''
* [[World Health Organization]], ''[http://www.who.int/csr/disease/marburg/en/ Marburg Haemorrhagic Fever]''.
*[http://www.ifrc.org/cgi/pdf_appeals.pl?/05/05me021.pdf#xml=http://www.ifrc.org/cgi/webinator/texis.exe/webinator/search/xml.txt?query=marburg&pr=english&order=r&cq=&id=4259e31f18 Red Cross PDF]
 
{{Viral diseases}}
[[Category:Biological weapons]]
[[Category:Biological weapons]]
[[Category:Hemorrhagic fevers]]
[[Category:Tropical diseases]]
[[Category:Viral diseases]]
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[[Category:Virus-related cutaneous conditions]]
[[Category:Zoonoses]]
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Latest revision as of 18:38, 19 October 2017

style="background:#Template:Taxobox colour;"|Marburg virus (MARV)
Transmission electron micrograph of Marburg virus
Transmission electron micrograph of Marburg virus
style="background:#Template:Taxobox colour;" | Virus classification
Group: Group V ((-)ssRNA)
Order: Mononegavirales
Family: Filoviridae
Genus: Marburgvirus
Species: Marburg marburgvirus
This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Marburg hemorrhagic fever.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:

Overview

Marburg virus (/ˈmɑːrbərɡ ˈvaɪrəs/ Template:Respell Template:Respell[1]) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. Marburg virus (MARV) causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever.[2] The virus is considered to be extremely dangerous. The WHO rates it as a Risk Group 4 Pathogen (requiring biosafety level 4-equivalent containment).[3] In the United States, the NIH/National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen[4] and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent.[5] It is also is listed as a biological agent for export control by the Australia Group.[6]

In 2009, expanded clinical trials of an Ebola and Marburg vaccine began in Kampala, Uganda.[7][8]

Discovery

Marburg virus was first described in 1967.[9] It was noticed during small outbreaks in the German cities Marburg and Frankfurt and the Yugoslav capital Belgrade in the 1960s. German workers were accidentally exposed to tissues of infected grivet monkeys (Chlorocebus aethiops) at the city's former main industrial plant, the Behringwerke, then part of Hoechst, and today of CSL Behring. During these outbreaks, 31 people became infected and seven of them died. MARV is a Select Agent,[10]

Nomenclature

The virus is one of two members of the species Marburg marburgvirus, which is included in the genus Marburgvirus, family Filoviridae, order Mononegavirales. The name Marburg virus is derived from Marburg (the city in Hesse, Germany, where the virus was first discovered) and the taxonomic suffix virus.[1]

According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Marburg virus is always to be capitalized, but is never italicized, and may be abbreviated (with MARV being the official abbreviation).

Marburg virus was first introduced under this name in 1967.[9] In 2005, the virus name was changed to Lake Victoria marburgvirus, which unfortunately was the same spelling as its species Lake Victoria marburgvirus.[11][12] However, most scientific articles continued to refer to Marburg virus. Consequently, in 2010, the name Marburg virus was reinstated and the species name changed.[1] A previous abbreviation for the virus was MBGV.

Human disease

Main article: Marburg virus disease

MARV is one of two marburgviruses that causes Marburg virus disease (MVD) in humans (in the literature also often referred to as Marburg hemorrhagic fever, MHF). Both viruses fulfill the criteria for being a member of the species Marburg marburgvirus because their genomes diverge from the prototype Marburg marburgvirus or the Marburg virus variant Musoke (MARV/Mus) by <10% at the nucleotide level.[1]

Recorded outbreaks

Marburg virus disease (MVD) outbreaks due to Marburg virus (MARV) infection
Year Geographic location Human Deaths/Cases (case-fatality rate)
1967 Marburg and Frankfurt, West Germany, and Belgrade, Yugoslavia 7/31 (23%)[9][13][14][15][16][17][18][19]
1975 Rhodesia and Johannesburg, South Africa 1/3 (33%)[20][21][22]
1980 Kenya 1/2 (50%)[23]
1987 Kenya 1/1 (100%)[24][25]
1988 Koltsovo, Soviet Union 1/1 (100%) [laboratory accident][26]
1990 Koltsovo, Soviet Union 0/1 (0%) [laboratory accident][27]
1998–2000 Durba and Watsa, Democratic Republic of the Congo ? (A total of 154 cases and 128 deaths of marburgvirus infection were recorded during this outbreak. The case fatality was 83%. Two different marburgviruses, MARV and Ravn virus (RAVV), cocirculated and caused disease. It has never been published how many cases and deaths were due to MARV or RAVV infection)[28][29][30]
2004–2005 Angola 227/252 (90%)[31][32][33][34][35][36][37]
2007 Uganda 1/3 (33%)[38][39]
2008 Uganda, Netherlands, USA 1/2 (50%)[40]
2012 Uganda 9/18 (50%)[41]
2014 Uganda 1/1 (100%)[42][43]

Virology

Genome

Like all mononegaviruses, marburgvirions contain non-infectious, linear nonsegmented, single-stranded RNA genomes of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a 5' cap, are not polyadenylated, and are not covalently linked to a protein.[44] Marburgvirus genomes are approximately 19 kb long and contain seven genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR.[45] The genomes of the two different marburgviruses (MARV and RAVV) differ in sequence.

Structure

File:Marburg em1986.png
CryoEM reconstruction of a section of the Marburg virus nucleocapsid. EMDB entry EMD-1986[46]

Like all filoviruses, marburgvirions are filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched.[45] Marburgvirions are generally 80 nm in width, but vary somewhat in length. In general, the median particle length of marburgviruses ranges from 795 to 828 nm (in contrast to ebolavirions, whose median particle length was measured to be 974–1,086 nm ), but particles as long as 14,000 nm have been detected in tissue culture.[47] Marburgvirions consist of seven structural proteins. At the center is the helical ribonucleocapsid, which consists of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane derived from the host cell membrane. The membrane anchors a glycoprotein (GP1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions in structure, marburgvirions are antigenically distinct.

Entry

Niemann–Pick C1 (NPC1) cholesterol transporter protein appears to be essential for infection with both Ebola and Marburg virus. Two independent studies reported in the same issue of Nature showed that Ebola virus cell entry and replication requires NPC1.[48][49] When cells from patients lacking NPC1 were exposed to Ebola virus in the laboratory, the cells survived and appeared immune to the virus, further indicating that Ebola relies on NPC1 to enter cells. This might imply that genetic mutations in the NPC1 gene in humans could make some people resistant to one of the deadliest known viruses affecting humans. The same studies described similar results with Marburg virus, showing that it also needs NPC1 to enter cells.[48][49] Furthermore, NPC1 was shown to be critical to filovirus entry because it mediates infection by binding directly to the viral envelope glycoprotein[49] and that the second lysosomal domain of NPC1 mediates this binding.[50]

In one of the original studies, a small molecule was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1.[49][51] In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse-adapted Ebola virus.[48] Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola antiviral drug.

Replication

The marburg virus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The virus RdRp partially uncoats the nucleocapsid and transcribes the genes into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Marburgvirus L binds to a single promoter located at the 3' end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3' end of the genome are transcribed in the greatest abundance, whereas those toward the 5' end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.[11]

Ecology

In 2009, the successful isolation of infectious MARV was reported from caught healthy Egyptian rousettes (Rousettus aegyptiacus).[38] This isolation, together with the isolation of infectious RAVV,[38] strongly suggests that Old World fruit bats are involved in the natural maintenance of marburgviruses. Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts. Recently the first experimental infection study of Rousettus aegyptiacus with MARV provided further insight into the possible involvement of these bats in MARV ecology.[52] Experimentally infected bats developed relatively low viremia lasting at least 5 days, but remained healthy and didn't develop any notable gross pathology. The virus also replicated to high titers in major organs (liver and spleen), and organs that might possibly be involved in virus transmission (lung, intestine, reproductive organ, salivary gland, kidney, bladder and mammary gland). The relatively long period of viremia noted in this experiment could possibly also facilitate mechanical transmission by blood sucking arthropods or infection of susceptible vertebrate hosts by direct contact with infected blood.

Biological weapon

The Soviet Union had an extensive offensive and defensive biological weapons program that included MARV.[53] At least three Soviet research institutes had MARV research programs during offensive times: the Virology Center of the Scientific-Research Institute for Microbiology in Zagorsk (today Sergiev Posad), the Scientific-Production Association "Vektor" (today the State Research Center of Virology and Biotechnology "Vektor") in Koltsovo, and the Irkutsk Scientific-Research Anti-Plague Institute of Siberia and the Far East in Irkutsk. As most performed research was highly classified, it remains unclear how successful the MARV program was. However, Soviet defector Ken Alibek claimed that a weapon filled with MARV was tested at the Stepnogorsk Scientific Experimental and Production Base in Stepnogorsk, Kazakh Soviet Socialist Republic (today Kazakhstan),[53] suggesting that the development of a MARV biological weapon had reached advanced stages. Independent confirmation for this claim is lacking. At least one laboratory accident with MARV, resulting in the death of Koltsovo researcher Nikolai Ustinov, occurred during offensive times in the Soviet Union and was first described in detail by Alibek.[53] After the dissolution of the Soviet Union, MARV research continued in all three institutes.[citation needed]

In popular culture

Template:Cleanup-list

  • In the non-fiction thriller, The Hot Zone, Richard Preston describes several MARV infections.
  • In the 2008 Indian science fiction movie Dasavathaaram by Kamal Haasan, the plot features an intended bio weapon of "Ebola Marburg" virus.
  • In the TV series Millennium, at the end of Season 2, a "prion version" of MARV causes a disease outbreak in Seattle, killing (amongst others) Frank Black's wife, Catherine. In the Season 3 episode "Collateral Damage", Peter Watt's daughter is infected with MARV by a Gulf War veteran who claims that the Millennium Group did the same to American soldiers during the first Gulf War.
  • In the crossover event of the TV series Medical Investigation, episode 17, and Third Watch, season 6 episode 16, Marburg virus disease breaks out in New York City, killing five of six infected people.
  • In the Sarah Jane Smith series (Series Two), MARV is used as a weapon by a doomsday cult.
  • In the short story Hell Hath Enlarged Herself by Michael Marshall Smith, one of the original scientists is infected with MARV in an attempt to test ImmunityWorks ver. 1.0.
  • In the novel Microserfs by Douglas Coupland, MARV is mentioned several times as a metaphor for the spread of information through the internet
  • In the novel Resident Evil: Caliban Cove, an insane scientist and former professor named Nicolas Griffith is referred to by Rebecca Chambers as having infected three men with MARV after they had been led to believe it was a harmless common cold virus.
  • In the novel Pandora's Legion by Harold Coyle and Barrett Tillman, an Al-Qaeda cell in Pakistan injects volunteers with MARV, who then board flights to major international airports in the western world where the large flow of people would facilitate the spreading of the virus into a pandemic.
  • In the TV series Body of Proof, Season 2, episodes 18 and 19 include a MARV outbreak.
  • In Mira Grant's novel Feed, a modified Marburg virus that cures cancer combines with a virally transmitted cure for the common cold, resulting in a virulent viral plague that turns infected humans and animals into zombies.
  • Motaba, the fictional deadly viral hemorrhagic fever, in the movie Outbreak, is based on MARV.
  • In the video game Trauma Team, the seventh chapter of the game, named "Patient Zero", has a storyline of a mass outbreak of the fictional Rosalia Virus, which has similar symptoms to the Ebola Virus and Marburg Virus.
  • In the episode "The Order 23 Job" of the TV show Leverage, the team's mark is led to believe that he is caught in an outbreak of weaponized Marburg virus made by the Soviets.
  • In the episode "Death Is in the Air" of the TV show Psych, the fictional Thornburg virus is based on the Marburg virus.
  • In the episode "Small Sacrifices" of the TV show "House MD", the team explores Marburg as a diagnosis for a patient
  • In the episode "The Promise" of the Canadian TV show ReGenesis Marburg was the subject of a war games exercise and a weaponized strain out of a lab in South Africa poses a potential threat.
  • In the episode "Honor Among Thieves" of the TV show Person of Interest, the Marburg virus is shown to be used as a potential bioterrorism agent to cause a pandemic starting in New York.
  • In the episode "I Am the Apocalypse" of the TV show Chicago Fire, a man with Marburg virus attempts to start an outbreak in a Chicago hospital.
  • In the TV series Bergerac, a potential Marburg outbreak is the subject of the episode "The Deadly Virus".

References

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  2. ↑ Spickler, Anna. "Ebolavirus and Marburgvirus Infections" (PDF).
  3. ↑ US Department of Health and Human Services. "Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition". Retrieved 2011-10-16.
  4. ↑ "Biodefense and Emerging Infectious Diseases". US National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH). Retrieved 2011-10-16.
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  6. ↑ The Australia Group. "List of Biological Agents for Export Control". Retrieved 2011-10-16.
  7. ↑ Beth Skwarecki Ebola, Marburg DNA Vaccines Prove Safe in Phase 1 Trial Medscape Medical News, September 17, 2014
  8. ↑ Evaluating an Ebola and a Marburg Vaccine in Uganda U.S. Department of Health & Human Services
  9. ↑ 9.0 9.1 9.2 PMID 4294540 (PMID 4294540)
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  10. ↑ US Animal and Plant Health Inspection Service (APHIS) and US Centers for Disease Control and Prevention (CDC). "National Select Agent Registry (NSAR)". Retrieved 2011-10-16.
  11. ↑ 11.0 11.1 Feldmann, H.; Geisbert, T. W.; Jahrling, P. B.; Klenk, H.-D.; Netesov, S. V.; Peters, C. J.; Sanchez, A.; Swanepoel, R.; et al. (2005). "Family Filoviridae". In Fauquet, C. M.; Mayo, M. A.; Maniloff, J.; Desselberger, U.; Ball, L. A. Virus Taxonomy—Eighth Report of the International Committee on Taxonomy of Viruses. San Diego, US: Elsevier/Academic Press. pp. 645–653. ISBN 0-12-370200-3
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  13. ↑ PMID 4168558 (PMID 4168558)
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  14. ↑ PMID 4296724 (PMID 4296724)
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  15. ↑ PMID 4966280 (PMID 4966280)
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  16. ↑ PMID 4966281 (PMID 4966281)
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  17. ↑ PMID 5005859 (PMID 5005859)
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  18. ↑ PMID 5748997 (PMID 5748997)
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  19. ↑ Stojkovic, L.; Bordjoski, M.; Gligic, A.; Stefanovic, Z. (1971). "Two Cases of Cercopithecus-Monkeys-Associated Haemorrhagic Fever". In Martini, G. A.; Siegert, R. Marburg Virus Disease. Berlin, Germany: Springer-Verlag. pp. 24–33. ISBN 978-0-387-05199-4
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  21. ↑ PMID 406394 (PMID 406394)
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  22. ↑ PMID 569445 (PMID 569445)
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  23. ↑ PMID 6122054 (PMID 6122054)
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  24. ↑ Marburg and Ebola viruses; Advances in Virus Research; Volume 47, 1996, Pages 1–52
  25. ↑ Known Cases and Outbreaks of Marburg Hemorrhagic Fever, in Chronological Order
  26. ↑ PMID 10024977 (PMID 10024977)
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  27. ↑ PMID 7941853 (PMID 7941853)
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  28. ↑ PMID 10546197 (PMID 10546197)
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  29. ↑ PMID 14720391 (PMID 14720391)
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  30. ↑ PMID 16943403 (PMID 16943403)
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  31. ↑ PMID 16038348 (PMID 16038348)
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  32. ↑ PMID 15917379 (PMID 15917379)
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  33. ↑ PMID 16775337 (PMID 16775337)
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  34. ↑ PMID 17940944 (PMID 17940944)
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  35. ↑ PMID 17940945 (PMID 17940945)
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  36. ↑ PMID 18838150 (PMID 18838150)
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  37. ↑ PMID 20441515 (PMID 20441515)
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  39. ↑ PMID 21987753 (PMID 21987753)
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  40. ↑ PMID 19751577 (PMID 19751577)
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  41. ↑ "Marburg hemorrhagic fever outbreak continues in Uganda". October 2012.
  42. ↑ "1st LD-Writethru: Deadly Marburg hemorrhagic fever breaks out in Uganda". October 5, 2014.
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  48. ↑ 48.0 48.1 48.2 Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR (September 2011). "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1". Nature. 477 (7364): 340–3. doi:10.1038/nature10348. PMC 3175325. PMID 21866103. Lay summary – New York Times.
  49. ↑ 49.0 49.1 49.2 49.3 Côté M, Misasi J, Ren T, Bruchez A, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J (September 2011). "Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection". Nature. 477 (7364): 344–8. doi:10.1038/nature10380. PMC 3230319. PMID 21866101. Lay summary – New York Times.
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  51. ↑ Flemming A (October 2011). "Achilles heel of Ebola viral entry". Nat Rev Drug Discov. 10 (10): 731. doi:10.1038/nrd3568. PMID 21959282.
  52. ↑ Paweska, J. T.; Jansen Van Vuren, P.; Masumu, J.; Leman, P. A.; Grobbelaar, A. A.; Birkhead, M.; Clift, S.; Swanepoel, R.; Kemp, A. (2012). "Virological and Serological Findings in Rousettus aegyptiacus Experimentally Inoculated with Vero Cells-Adapted Hogan Strain of Marburg Virus". PLoS ONE. 7 (9): e45479. doi:10.1371/journal.pone.0045479. PMC 3444458. PMID 23029039. open access publication – free to read
  53. ↑ 53.0 53.1 53.2 Alibek, Steven; Handelman. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from Inside by the Man Who Ran It. New York: Random House. ISBN 0-385-33496-6

Further reading

  • Klenk, Hans-Dieter (1999). Marburg and Ebola Viruses. Current Topics in Microbiology and Immunology, vol. 235. Berlin, Germany: Springer-Verlag. ISBN 978-3-540-64729-4
  • Klenk, Hans-Dieter; Feldmann, Heinz (2004). Ebola and Marburg Viruses: Molecular and Cellular Biology. Wymondham, Norfolk, UK: Horizon Bioscience. ISBN 978-1-904933-49-6
  • Kuhn, Jens H. (2008). Filoviruses: A Compendium of 40 Years of Epidemiological, Clinical, and Laboratory Studies. Archives of Virology Supplement, vol. 20. Vienna, Austria: SpringerWienNewYork. ISBN 978-3-211-20670-6
  • Martini, G. A.; Siegert, R. (1971). Marburg Virus Disease. Berlin, Germany: Springer-Verlag. ISBN 978-0-387-05199-4.
  • Ryabchikova, Elena I.; Price, Barbara B. (2004). Ebola and Marburg Viruses: A View of Infection Using Electron Microscopy. Columbus, Ohio, US: Battelle Press. ISBN 978-1-57477-131-2

External links

Template:Filoviridae

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