Enterovirus 71 (EV71), also known as Enterovirus A71 (EV-A71), is a virus of the genus Enterovirus in the Picornaviridae family, notable for its role in causing epidemics of severe neurological disease and hand, foot, and mouth disease in children. It was first isolated and characterized from cases of neurological disease in California in 1969. Enterovirus 71 infrequently causes polio-like syndrome permanent paralysis.
Evolution
This virus is a member of the enterovirus species A. Species A was formerly assigned to the genus Rhinovirus. This virus appears to have evolved only recently with the first known strain isolated in 1965. It was associated with an outbreak of neurological disease in the United States in 1969. It then spread to Europe with outbreaks there in Bulgaria (1975) and Hungary (1978). It has since spread to various countries in Asia where it has been responsible for several outbreaks, most recently in Cambodia (2012).
The strains fall into six genogroups named A to F. Both the B and C genogroups have been subdivided into B0–B5 and C1–C5. The genogroup C appears to have evolved ~1970 while the A and B taxa evolved prior to this. Genogroup D was identified in India only and genogroups E and F in Africa only. Phylogenetic studies performed on partial sequences of viruses from India suggest that additional genogroups exist.
An analysis of strains isolated in Europe (Austria, France and Germany) showed that the clades C1b and C2b originated in 1994 (95% confidence interval 1992.7–1995.8) and 2002 (95% confidence interval 2001.6–2003.8), respectively.
Intra- and inter-typic recombination occur commonly in EV-A71 virus infections. Recombination can occur when at least two viral genomes are present in the same host cell. The mechanism of recombination likely involves strand switching by the RNA-dependent RNA polymerase (copy-choice recombination), a mechanism demonstrated in poliovirus. In addition to being a source of sequence diversity, recombination in RNA viruses appears to be an adaptation for repairing genome damage.
Virology
The receptors for EV71 and CVA16 have been identified as P-selectin glycoprotein ligand-1 and scavenger receptor class B, member 2 (SCARB2); both are transmembrane proteins.
The basic reproductive number (R0) for enterovirus 71 (EV71) was estimated to a median of 5.48 with an interquartile range of 4.20 to 6.51.
Treatment
There is no antiviral agent known to be effective in treating EV71 infection. However, Sinovac Biotech Ltd., a pharmaceutical company in China, conducted an experimental trial for an EV71 vaccination, which was completed in March 2013. In December 2015, the China Food and Drug Administration (CFDA) approved the first EV71 vaccine. The vaccine was administered to approximately 10,000 children between the ages of 6 and 35 months. Of the placebo group, there were 30 cases of hand, foot, and mouth disease (HFMD) reported, and 41 cases of any EV71-associated illness. This can be compared to only 3 cases of HFMD and eight cases of any EV71-related illness reported in the vaccine group. Participants were surveilled from day 56 until the end of the 14-month experiment period, in addition to checkups at months five, eight, eleven, and fourteen. Other experimental vaccines and antiviral agents are being researched. For example, "both bovine and human lactoferrins were found to be potent inhibitors of EV71 infection" and "ribavirin could be a potential anti-EV71 drug."
Research
A joint UK and Chinese team working at the UK's national synchrotron facility near Oxford determined the structure of EV71 in 2012. Researchers observed movements resembling breathing in the virus, and found that this accompanied the infection process, together with a small molecule picked up from the body's cells and used to switch state. This particular molecule must be discarded in order to start an infection, and new research will be aimed at creating a synthetic replica that would bond strongly to the virus and stop the infection process.
Outbreaks
Australia
In June 2013, an outbreak of four cases was noted in Sydney. Approximately 100 more children are believed to have been infected, and a panel of doctors are monitoring the situation at present.