An analogous division of 3Dpol sequences into the 15 clades by phylogenetic analysis was similarly supported by their distribution of pairwise distances (see Fig. the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization. == INTRODUCTION == Enterovirus 71 (EV71) is one of the most frequently detected pathogenic human enteroviruses, responsible for large-scale epidemic occurrences of neurological disease throughout Southeast Asia (51,58). EV71 contains a single-stranded, positive-sense RNA genome and is classified as a member of species A (EV-A) in theEnterovirusgenus of thePicornaviridaefamily (60). As with other EV-A enteroviruses, EV71 is transmitted by the fecal-oral route and normally causes subclinical or relatively Impulsin mild, self-limiting Rabbit Polyclonal to AQP3 infections, such as hand, foot, and mouth disease (HFMD) (65). However, unlike other users of EV-A, EV71 infections are connected in a small proportion of subjects with a wide array of severe disease presentations, including aseptic meningitis, encephalitis, and acute flaccid paralysis (AFP) (examined in referrals29and58). Severe and fatal EV71 infections are mainly found in young children, with male individuals outnumbering Impulsin female individuals (12,52). Impulsin There has been a considerable increase in the rate of recurrence and severity of EV71 epidemics in recent years, particularly in the Asian Pacific region (5,13,58,65), prompting urgent, ongoing investigations of the virological and sponsor factors contributing to the apparently increasing pathogenicity of the disease (5,11,58). Substantial insights into the development and molecular epidemiology of circulating strains and genotypes of EV71 from many of the most-affected countries have been obtained through analysis of structural genome areas, principally VP1. EV71 has been classified into a total of three genogroups (Ggs), designated GgA to GgC (6), showing approximately 13 to 20% amino acid sequence divergence from each other in the VP1 region (6,28) and estimated to have originated from a common ancestor as recently as 1941 (61). Several studies possess investigated whether different genogroups or subgenogroups vary in their pathogenicity, which might then clarify the variability in results of EV71 infections in different decades and between continents. While whole-genome sequence comparisons of EV71 strains isolated from severe or fatal instances of EV71 illness showed no reproducible variations from those causing more mild infections (54,57), specific associations of GgC2 variants with severe neurological disease and of B3 with HFMD or slight/inapparent infections were observed during an outbreak in Perth, Australia, in 1988, when both genogroups were cocirculating (35,36). More recently, a greater probability of GgC5 to cause neurological complications than GgC4 was reported (44). In the current study we genetically characterized a large number of EV71 strains, collected from South and East Asia, Australia, and Europe, in the VP1 region and a distal region of the genome (part of the 3D polymerase-encoding region [3Dpol]) for recognition of recombination events. Recombination is definitely a frequently recorded trend in picornaviruses and contributes to their evolutionary diversity as well as a means to acquire fresh phenotypic qualities from acquisition of novel combination of structural and nonstructural genes and 5-untranslated region (5-UTR) sequences. Recombination in picornaviruses was first observed between serotypes of poliovirus in vaccine recipients (8,20,39) and more recently in a wide range of human being enteroviruses (1,15,16,21,31,41,43,45,48,56), foot-and-mouth disease disease (FMDV), and teschoviruses (55) and, more recently, parechoviruses (3,4). In each disease, recombination breakpoints concentrate in the 2A region, although further sites happen in P2 and P3 genes.
An analogous division of 3Dpol sequences into the 15 clades by phylogenetic analysis was similarly supported by their distribution of pairwise distances (see Fig