The major etiological agents that cause HFMD are the human enteroviruses species A<br>(HEV-A), particularly coxsackievirus A16 (CA16) and enterovirus 71 (EV71). These<br>belong to the genus Enterovirus within the family Picornaviridae. Other HEV-A<br>serotypes, such as Coxsackievirus A6 and Coxsackievirus A10, are also associated with<br>HFMD and herpangina. While all these viruses can cause mild disease in children,<br>EV71 has been associated with neurological disease and mortality in large outbreaks in<br>the Asia Pacific region over the last decade (1–4).<br>Enteroviruses are small viruses with virions that are about 30 nm in diameter and<br>composed of four structural proteins called VP1, VP2, VP3 and VP4. VP1 is the major<br>capsid protein on the surface of the virion, while VP4 is not exposed on the surface.<br>Serotyping of human enteroviruses has traditionally been based on neutralization tests<br>using specific antiserum pools: as such they are directed particularly at serological<br>responses to the VP1 protein. More recently, due in part to limited access to serotyping<br>antisera and improved accessibility to molecular technology, there has been a move<br>towards using molecular typing methods. The gene encoding VP1 is the target gene<br>most often used in molecular typing methods for enteroviruses. It is for this reason<br>that a wealth of genetic sequence data on EV71 is available, enabling the genetic<br>classification of virus strains in common circulation (5–7).<br>Ribonucleic acid (RNA) viruses, such as the enteroviruses, generate evolutionary<br>changes fairly rapidly. Labels (genogroups) can be applied to clusters of epidemiologically<br>related EV71 strains, generally those with up to a 5% nucleotide difference in the VP1<br>region. These genogroup divisions have no known significance for any enterovirus<br>other than being a convenient label to reflect viral sequence clustering within a sea of<br>genetic diversity. It is important to note that there is not yet evidence of any association<br>between virulence and particular genogroups or subgenogroups of EV71.<br>Figure 1 on the succeeding page shows a phylogenetic tree containing the three<br>genogroups của EV71: genogroups A, B và C. Virus EV71 nguyên mẫu là BrCr, bị cô lập <br>ở California vào năm 1969. Đây là loại virus được lấy mẫu duy nhất của genogroup Một
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