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Enterovirus

Genus of viruses

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Serologic studies have distinguished 71 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the basis of reduced or nonreciprocal cross-neutralization between variant strains. On the basis of their pathogenesis in humans and animals, the enteroviruses were originally classified into four groups, polioviruses, Coxsackie A viruses (CA), Coxsackie B viruses (CB), and echoviruses, but it was quickly realized that there were significant overlaps in the biological properties of viruses in the different groups. Enteroviruses isolated more recently are named with a system of consecutive numbers: EV-D68, EV-B69, EV-D70, EV-A71, etc., where genotyping is based on the VP1 capsid region.

Enteroviruses affect millions of people worldwide each year and are often found in the respiratory secretions (e.g., saliva, sputum, or nasal mucus) and stool of an infected person. Historically, poliomyelitis was the most significant disease caused by an enterovirus, namely poliovirus. There are 81 non-polio and 3 polio enteroviruses that can cause disease in humans. Of the 81 non-polio types, there are 22 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, and 25 other enteroviruses.

Poliovirus, as well as coxsackie and echovirus, is spread through the fecal–oral route. Infection can result in a wide variety of symptoms, including those of: mild respiratory illness (the common cold), hand, foot and mouth disease, acute hemorrhagic conjunctivitis, aseptic meningitis, myocarditis, severe neonatal sepsis-like disease, acute flaccid paralysis, and the related acute flaccid myelitis.

Virology

Enteroviruses are members of the picornavirus family, a large and diverse group of small RNA viruses characterized by a single positive-strand genomic RNA. All enteroviruses contain a genome of approximately 7,500 bases and are known to have a high mutation rate due to low-fidelity replication and frequent recombination. After infection of the host cell, the genome is translated in a cap-independent manner into a single polyprotein, which is subsequently processed by virus-encoded proteases into the structural capsid proteins and the nonstructural proteins, which are mainly involved in the replication of the virus.

RNA recombination appears to be a major driving force in the evolution of enteroviruses as well as in the shaping of their genetic architecture. The mechanism of recombination of the RNA genome likely involves template strand switching during RNA replication, a process known as copy choice recombination. RNA recombination is considered to be an adaptation for dealing with RNA genome damage and a source of genetic diversity. It is also a source of concern for vaccination strategies, because live attenuated/mutated strains used for vaccination could potentially recombine with wild-type related strains, as has been the case with circulating vaccine derived polio viruses (cVDPDs). The capsid region and especially VP1 is a recombination coldspot, and this is one of the main reasons to use this region for genotyping. However, the 5'UTR - capsid junction and the beginning of the P2 region have been observed to recombine very frequently, although recombinations do occur in the rest of the genome as well. Interestingly, the enterovirus species EV-A, EV-B, EV-C, EV-D have not been observed so far to exchange genomic regions among them, with the exception of the 5'UTR.

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