Hantavirus infection classification
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Basir Gill, M.B.B.S, M.D.[2] Usama Talib, BSc, MD [3]
Overview
Hantavirus infection can be classified based on taxonomic classification of the virus, clinical syndrome, and phylogenetic host association. The family Hantaviridae (class Bunyaviricetes, order Elliovirales) encompasses seven genera and 53 species, with all human-pathogenic hantaviruses belonging to the genus Orthohantavirus within the subfamily Mammantavirinae.[1][2] The two major clinical syndromes are hemorrhagic fever with renal syndrome (HFRS), caused by Old World hantaviruses in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS), also called hantavirus pulmonary syndrome (HPS), caused by New World hantaviruses in the Americas.[3] Although HFRS and HCPS are recognized as distinct clinical entities, there are overlapping symptoms, signs, and pathogenic alterations.[3] Nephropathia epidemica (NE) is a mild form of HFRS caused primarily by Puumala virus.[3]
Classification
Taxonomic Classification
Hantaviruses belong to the family Hantaviridae, which was reclassified in 2024 under the order Elliovirales, class Bunyaviricetes (previously order Bunyavirales).[2] The family encompasses seven genera and 53 species.[4] All human-pathogenic hantaviruses belong to the genus Orthohantavirus within the subfamily Mammantavirinae.[1] The family also includes subfamilies Actantavirinae (reptile-associated) and Repantavirinae (fish-associated), as well as genera Loanvirus, Mobatvirus, and Thottimvirus (associated with shrews, moles, and bats).[1][5]
Hantavirids produce enveloped virions (80–120 nm in diameter) containing three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-dependent RNA polymerase (RdRP) domain.[1] The total genome size is approximately 10.5–14.6 kb.[1]
| Taxonomic Rank | Classification |
|---|---|
| Realm | Riboviria |
| Kingdom | Orthornavirae |
| Phylum | Negarnaviricota |
| Subphylum | Polyploviricotina |
| Class | Bunyaviricetes |
| Order | Elliovirales |
| Family | Hantaviridae |
| Subfamily (human-pathogenic) | Mammantavirinae |
| Genus (human-pathogenic) | Orthohantavirus |
Adapted from ICTV Virus Taxonomy Profile: Hantaviridae 2024.[1][2]
Clinical Syndrome-Based Classification
Hantavirus infection can be classified on the basis of the clinical manifestations and the type of hantavirus responsible for the manifestation. The clinical manifestations include hantavirus cardiopulmonary syndrome (HCPS), hemorrhagic fever with renal syndrome (HFRS), and nephropathia epidemica (NE).[3][6]
HFRS is endemic in Europe and Asia and is characterized by increased vascular permeability, coagulopathy, and acute kidney injury. The disease course may include five phases: febrile, hypotensive, oliguric, diuretic, and convalescent.[3] HFRS-causing hantaviruses include Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), Puumala virus (PUUV), Seoul virus (SEOV), and Tula virus (TULV, rare).[3]
HCPS (also called hantavirus pulmonary syndrome, HPS) is endemic in the Americas and is characterized by respiratory failure and cardiogenic shock. HCPS begins with a febrile prodrome followed by a cardiopulmonary phase with sudden onset of cough, dyspnea, tachycardia, and hypotension, leading to non-cardiogenic pulmonary edema.[3] The most common causes are Sin Nombre virus (SNV) in North America and Andes virus (ANDV) in South America.[3]
NE (nephropathia epidemica) is a mild form of HFRS caused primarily by Puumala virus (PUUV), with a case fatality rate (CFR) 1%.[3][7]
Although HFRS and HCPS are recognized as distinct clinical entities, there are overlapping symptoms, signs, and pathogenic alterations. Both syndromes can lead to renal failure, and virtually all patients with HCPS and more than half of patients with HFRS have respiratory symptoms.[3]
Classification by Virus, Host, Geography, and Clinical Syndrome
Hantavirus Cardiopulmonary Syndrome (HCPS)
The most severe forms of HCPS are associated with Sin Nombre virus, Andes virus, Araraquara virus, and Juquitiba virus, all with CFRs between 30% and 45%. Choclo virus (CHOV) and Laguna Negra virus (LANV) have a CFR between 12% and 15%.[3] Andes virus is unique among hantaviruses for documented person-to-person transmission.[3]
| Virus | Abbreviation | Primary Rodent Host | Geographic Distribution | CFR |
|---|---|---|---|---|
| Sin Nombre virus | SNV | Peromyscus maniculatus (deer mouse) | North America (western USA, Canada) | ~36% |
| Andes virus | ANDV | Oligoryzomys longicaudatus (long-tailed colilargo) | Argentina, Chile | 30–45% |
| Araraquara virus | ARAV | Necromys lasiurus | Brazil | 30–45% |
| Juquitiba virus | JUQV | Oligoryzomys nigripes | Brazil, Argentina | 30–45% |
| New York virus | NYV | Peromyscus leucopus (white-footed mouse) | North America (eastern USA) | — |
| Monongahela virus | MGLV | Peromyscus leucopus | North America (eastern USA) | — |
| Bayou virus | BAYV | Oryzomys palustris (marsh rice rat) | North America (southeastern USA) | — |
| Black Creek Canal virus | BCCV | Sigmodon hispidus (hispid cotton rat) | North America (southeastern USA) | — |
| Muleshoe virus | MULEV | Sigmodon hispidus | North America | — |
| Choclo virus | CHOV | Oligoryzomys fulvescens | Panama | 12–15% |
| Laguna Negra virus | LANV | Calomys callosus | Argentina, Paraguay, Bolivia | 12–15% |
| Bermejo virus | BMJV | Oligoryzomys chacoensis, O. flavescens | Bolivia, Argentina | — |
| Lechiguanas virus | LECV | Oligoryzomys flavescens | Argentina | — |
| Oran virus | ORNV | Oligoryzomys chacoensis | Argentina | — |
| Maciel virus | MCLV | Bolomys obscurus | Argentina | — |
| Castelo Dos Sonhos virus | CASV | Oligoryzomys spp. | Brazil | — |
Adapted from Vial et al. 2023,[3] Jiang et al. 2017,[6] and Avšič-Županc et al. 2019.[7] CFR = case fatality rate. "—" indicates insufficient data for reliable CFR estimate.
Hemorrhagic Fever with Renal Syndrome (HFRS)
HFRS caused by Hantaan virus, Amur virus, and Dobrava-Belgrade virus (genotype Dobrava) are more severe, with mortality rates from 5% to 15%, whereas Seoul virus causes moderate disease and Puumala virus and Saaremaa virus (DOBV-Aa genotype) cause mild forms of disease with mortality rates 1%.[7][3]
| Virus | Abbreviation | Primary Rodent Host | Geographic Distribution | Severity / CFR |
|---|---|---|---|---|
| Hantaan virus | HTNV | Apodemus agrarius (striped field mouse) | China, Russia, Korea | Severe; CFR 5–15% (historically), ~1–1.3% (modern) |
| Amur virus | AMRV | Apodemus peninsulae (Korean field mouse) | China, Russia, Korea | Severe; CFR 5–15% |
| Dobrava-Belgrade virus (genotype Dobrava, DOBV-Af) | DOBV | Apodemus flavicollis (yellow-necked mouse) | Balkans, southeastern Europe | Severe; CFR 10–12% |
| Dobrava-Belgrade virus (genotype Sochi, DOBV-Ap) | DOBV-Ap | Apodemus ponticus (Black Sea field mouse) | Southern Russia (Sochi district) | Moderate to severe |
| Dobrava-Belgrade virus (genotype Kurkino) | DOBV-Kurkino | Apodemus agrarius (striped field mouse) | Central Europe (Germany, Poland, Lithuania) | Mild; no lethal outcomes reported |
| Saaremaa virus (DOBV-Aa genotype) | SAAV | Apodemus agrarius (striped field mouse) | Estonia, Russia, Finland, Germany, Denmark, Slovenia | Mild; CFR 1% |
| Seoul virus | SEOV | Rattus norvegicus (brown rat), R. rattus | Global (via international shipping) | Moderate; CFR 1–2% |
| Puumala virus | PUUV | Myodes glareolus (bank vole) | Northern/western Europe, Russia | Mild (NE); CFR 1% (0.1–0.4%) |
| Thailand hantavirus | THAIV | Bandicota indica | Thailand | Rare; limited data |
| Tula virus | TULV | Microtus arvalis (common vole) | Europe | Very rare; only a few human cases reported |
Adapted from Vial et al. 2023,[3] Avšič-Županc et al. 2019,[7] Vaheri et al. 2013,[8] and Klempa et al. 2013.[9] CFR = case fatality rate.
Nephropathia Epidemica (NE)
Nephropathia epidemica is a mild form of HFRS caused primarily by Puumala virus (PUUV) and, to a lesser extent, by the Saaremaa virus (DOBV-Aa genotype). NE is the most common hantavirus disease in Europe, with Finland reporting the highest number of cases.[3][8]
| Virus | Primary Rodent Host | Geographic Distribution |
|---|---|---|
| Puumala virus (PUUV) | Myodes glareolus (bank vole) | Northern/western Europe, Russia, Finland |
| Saaremaa virus (DOBV-Aa) | Apodemus agrarius (striped field mouse) | Estonia, central/eastern Europe |
Dobrava-Belgrade Virus Genotype Classification
Dobrava-Belgrade virus (DOBV) has a complex taxonomy with four recognized genotypes that differ in phylogeny, host reservoir, geographic distribution, and pathogenicity for humans:[9][8]
| Genotype | Alternate Name | Rodent Host | Geography | Pathogenicity |
|---|---|---|---|---|
| Dobrava (DOBV-Af) | DOBV | Apodemus flavicollis (yellow-necked mouse) | Balkans, southeastern Europe | Severe; CFR up to 12% |
| Kurkino | DOBV-Kurkino | Apodemus agrarius (striped field mouse) | Central Europe (Germany, Poland, Lithuania, Czech Republic) | Mild; no lethal outcomes reported |
| Sochi (DOBV-Ap) | DOBV-Ap | Apodemus ponticus (Black Sea field mouse) | Southern Russia (Sochi district) | Moderate to severe |
| Saaremaa (DOBV-Aa) | SAAV | Apodemus agrarius (striped field mouse) | Estonia, Russia, Finland, Germany, Denmark, Slovenia, Croatia, Slovakia | Mild |
Adapted from Klempa et al. 2013[9] and Vaheri et al. 2013.[8]
Phylogenetic Host-Based Classification
A newer framework proposes classifying orthohantaviruses into three phylogenetically based rodent host groups rather than the traditional Old World versus New World geographic dichotomy. This framework better accounts for the fact that related arvicoline rodents and their orthohantaviruses are found in both hemispheres, making the geographic dichotomy imprecise.[10]
| Host Group | Rodent Subfamily/Family | Representative Viruses | Geography | Primary Syndrome |
|---|---|---|---|---|
| Murinae-associated | Family Muridae | HTNV, SEOV, DOBV | Asia, Europe | HFRS |
| Arvicolinae-associated | Subfamily of Cricetidae | PUUV, Tula virus | Europe, parts of North America | Mild HFRS / NE |
| Sigmodontinae/Neotominae-associated | Subfamily of Cricetidae | SNV, ANDV, and other New World viruses | Americas | HCPS |
Adapted from Mull et al. 2023.[10]
There are currently 58 distinct orthohantaviruses recognized, with over 24 recognized as pathogenic to humans. Case fatality of pathogenic orthohantaviruses ranges from 0.1% to 50%.[10]
Epidemiological Summary
Approximately 200,000 cases of hantavirus infection are reported worldwide per year.[10] Key epidemiological data by region include:
China: A mean of 12,800 HFRS cases per year (2004–2016), with a CFR of 1.3%.[3]
European Union: A mean of 3,100 HFRS cases per year; Finland reports 43%, Germany 30%, and Sweden 6% of all cases. CFR ranges from 0.03% (Germany) to 0.4% (Sweden) for PUUV, and 10–12% for DOBV in the Balkans.[3]
Russia: Approximately 7,300 HFRS cases per year, with an overall CFR of 0.4%.[3]
Americas: Approximately 300 HCPS cases per year, mainly in Argentina, Brazil, and Chile.[3]
South Korea: 300–600 cases per year; CFR has decreased from 5–7% (1950s) to 1% (2011–2016).[3]
From serosurveillance studies in Finland, only around 15% of infected people are diagnosed and reported.[3] The incubation period ranges from 2 to 6 weeks.[3] Transmission mainly occurs via inhalation of aerosolized rodent excreta (urine, feces, saliva). Person-to-person transmission has been documented only for Andes virus.[3]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Bradfute SB, Calisher CH, Klempa B, Klingström J, Kuhn JH, Laenen L, Maes P, Papa A, Schmaljohn CS, Tischler ND, Plyusnin A (2024). "ICTV Virus Taxonomy Profile: Hantaviridae 2024". J Gen Virol. 105 (4). doi:10.1099/jgv.0.001975. PMID 38587456 Check
|pmid=value (help). - ↑ 2.0 2.1 2.2 Kuhn JH, Brown K, Adkins S, de la Torre JC, Digiaro M, Ergünay K, Forber PJ, Goldbach RW, Grybchuk D, Hughes HR, Junglen S, Klempa B, Krupovic M, Lambert AJ, Maes P, Marklewitz M, Mielke-Ehret N, Mirazimi A, Mühlbach HP, Palacios G, Pawęska JT, Peters CJ, Plyusnin A, Rubbenstroth D, Shi M, Siddell SG, Simmonds P, Sironi M, Smagghe G, Tesh RB, Turina M, Wahl V, Walker PJ, Wang L, Whitfield AE, Yeh SD, Zerbini FM, Zhang YZ (2024). "Promotion of Order Bunyavirales to Class Bunyaviricetes to Accommodate a Rapidly Increasing Number of Related Polyploviricotine Viruses". J Virol. 98 (10): e0106924. doi:10.1128/jvi.01069-24. PMID 39303014 Check
|pmid=value (help). - ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 Vial PA, Ferrés M, Vial C, Klingström J, Ahlm C, López R, Le Corre N, Mertz GJ (2023). "Hantavirus in Humans: A Review of Clinical Aspects and Management". Lancet Infect Dis. 23 (9): e371–e382. doi:10.1016/S1473-3099(23)00128-7. PMID 37105214 Check
|pmid=value (help). - ↑ Chen RX, Gong HY, Wang X, Zhang L, Bao DL (2023). "Zoonotic Hantaviridae With Global Public Health Significance". Viruses. 15 (8): 1705. doi:10.3390/v15081705. PMID 37632047 Check
|pmid=value (help). - ↑ Laenen L, Vergote V, Calisher CH, Klempa B, Klingström J, Kuhn JH, Maes P (2019). "Hantaviridae: Current Classification and Future Perspectives". Viruses. 11 (9): E788. doi:10.3390/v11090788. PMID 31461937.
- ↑ 6.0 6.1 Jiang H, Zheng X, Wang L, Du H, Wang P, Bai X (2017). "Hantavirus infection: a global zoonotic challenge". Virol Sin. 32 (1): 32–43. doi:10.1007/s12250-016-3899-x. PMID 28120221.
- ↑ 7.0 7.1 7.2 7.3 Avšič-Županc T, Saksida A, Korva M (2019). "Hantavirus Infections". Clin Microbiol Infect. 21S: e6–e16. doi:10.1111/1469-0691.12291. PMID 24750436.
- ↑ 8.0 8.1 8.2 8.3 Vaheri A, Henttonen H, Voutilainen L, Mustonen J, Sironen T, Vapalahti O (2013). "Hantavirus infections in Europe and their impact on public health". Rev Med Virol. 23 (1): 35–49. doi:10.1002/rmv.1722. PMID 23280975.
- ↑ 9.0 9.1 9.2 Klempa B, Avsic-Zupanc T, Clement J, Dzagurova TK, Henttonen H, Heyman P, Jakab F, Kruger DH, Maes P, Papa A, Tkachenko EA, Ulrich RG, Vapalahti O, Vaheri A (2013). "Complex Evolution and Epidemiology of Dobrava-Belgrade Hantavirus: Definition of Genotypes and Their Characteristics". Arch Virol. 158 (3): 521–9. doi:10.1007/s00705-012-1514-5. PMID 23090188.
- ↑ 10.0 10.1 10.2 10.3 Mull N, Seifert SN, Forbes KM (2023). "A Framework for Understanding and Predicting Orthohantavirus Functional Traits". Trends Microbiol. 31 (11): 1102–1110. doi:10.1016/j.tim.2023.05.004. PMID 37277284 Check
|pmid=value (help).