Enterovirus 68

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2] Vidit Bhargava, M.B.B.S [3]

style="background:#Template:Taxobox colour;"|Enterovirus 68
style="background:#Template:Taxobox colour;" | Virus classification
Group: Group IV ((+)ssRNA) Family: Picornaviridae Genus: Enterovirus Species: Enterovirus D
Subtype
Enterovirus 68
Synonyms
Human rhinovirus 87

Overview

Enterovirus 68 (EV68, EV-D68) is a member of the Picornaviridae family, an enterovirus. It is a non-enveloped, positive sense ssRNA virus. It is distributed more in the pediatric age group, not just in USA but in other countries around the world as well. While enteroviruses can cause a wide range of symptoms ranging from mild febrile illness to fatal meningitis and encephalitis, EV-68 is mostly associated with respiratory symptoms. Recently, EV-68 was isolated from 2 children with a polio like flaccid paralysis. However, in 3 more kids with a similar presentation the virus could not be isolated.

Origin and serotypes

Enteroviruses were divided into four subgroups based on the diseases they cause in humans. The Four subgroups were polioviruses, coxsackie A viruses, coxsackie B viruses, and echovirus. However, on further studies it was found and understood that, some coxsackie and echoviruses had overlapping antigenic properties with respect to the diseases they caused in mice. As a result, they were all later described as enteroviruses and numbered sequentially, beginning with enterovirus 68 (EV68). Current classifications systems are based on molecular, antigenic as well as biological properties of these viruses. The enterovirus family is presently subgrouped into 5 categories: Poliovirus, Human enterovirus A (HEV-A), HEV-B, HEV-C and HEV-D. Enterovirus 68 is one of the 3 serotypes in HEV-D subgroup.

EV68 first came into picture when it caused pneumonia and bronchiolitis in four children in California in 1962. Ten times EV68 has been isolated the most recent being 2014. The other isolations were in the years 1970, 1987, 1994, 1997, 2000 and 2003. Antigen typing reagents are not available in all facilities and hence EV68 involvement might be underestimated.

Human rhinovirus 87 was isolated at the same time as EV68. Corn is a prototype of HRV87 and is very unique in its receptor quality. Cross neutralization and partial capsid sequence studie shave revealed that HRV-87 Corn belongs to the same group as EV68.

A study on 1962 isolates of EV68 have shown genome sequences of the 5′-non-translated (NTR) and 3D polymerase coding regions and complete VP1 capsid protein coding region sequence.

Epidemiology

Enterovirus 68 infection is an extremely rare condition, CDC found a total of 26 cases from 1987-2005, the most being 11 in the year 2003. The first ever case was discovered in the year 1962 in California from four children with pneumonia and bronchioloitis and since then only a few cases have been discovered, however there have been recent outbreaks in other parts of the world as well. Recently, five cases of unexplained paralysis were reported in California. In two of these enteroviruses were isolated.

Philippines: During October 2008-March 2009, an outbreak of HEV68 was detected in the Eastern Visayas region of the Philippines among pediatric patients hospitalized with pneumonia.

Japan: In Japan, first cases were picked up in the year 2005. Since 2005 to 2010 < 10 cases were discovered almost every year, till 2010 where almost 120 cases occurred. Most of these presented with an acute respiratory illness with cough, breathing difficulty, wheezing etc.

Netherlands: In 2010, all patients with pneumonia and pneumonia like symptoms were prospectively studied and their samples were sequenced. A total of 24 of these were found to be due to enterovirus 68. 50% of them being in the age group < 20 years.

Identification of Isolates

Oberste etal used rabbit antisera for typing of isolates. To the isolates, serotype specific rabbit antisera was added. Other method used for sequencing was partial sequencing of VP1 capsid gene, using primer 292 (5'-MIGCIGYIGARACNGG-3') and 222 (5'-CICCIGGIGGIAYRWACAT-3'). The serotype was determined by comparing partial sequence of isolates with a database containing partial sequences of all known enterovirus serotypes as described previously by the same group.

Two commercially available, FDA approved multipathogen detection systems - Luminex xTAG RVP and Idaho Technologies (Salt Lake City, Utah) Film array respiratory panel are currently being used in the united states. Both use broadly reactive primers that can pick up both enterovirus as well as human rhinovirus.

Life cycle

Enterovirus 68 is acid labile and prefers a lower temperature, whereas rhinoviruses are more acid stable and can survive at higher temperatures. In a study to predict the effect of acidity and temperature on viral growth, 5 clinical isolates were tested for acid stability versus EV-68 FERMON strain. It was shown that all strains showed 100-1000 fold reduction in infectivity titres, after incubation for 1 hour in pH 3 buffer. The results were in agreement with a similar study done by Blomqvist et al. Also, in the study each of EV 68 strains also grew to a lower titre at 37 °C than at 33 °C. It is due to this survivability at lower temperatures and higher pH that most strains are isolated from respiratory specimens.

Pathogenesis

The clinical sign & symptoms of enterovirus 68 range from mild illness to more severe complications that require hospitalization and in rare cases have been fatal. Major symptoms associated with enterovirus infection includes pharyngeal congestion, headache, myalgia, chills, and sore throat but not increased respiratory rate or difficulty breathing. In a few cases associated specifically with enterovirus 68 some respiratory difficulty along with other symptoms wwas observed. Most symptomatic cases were amongst the younger age groups.