Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries

Abstract

Human enterovirus 71 (EV-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. Uncertainty persists regarding the circulation of virus populations in several geographical areas and the timescale of their dissemination. We determined EV-71 sequences at loci 1D (VP1 capsid protein) and 3CD (nonstructural proteins) in 86 strains recovered in Austria, France and Germany and performed an evolutionary genetic study of extant virus populations. Phylogenetic analyses positioned 78 of the 86 sequences within two clades among subgenogroups C1 and C2. A minor sequence cluster was assigned to subgenogroup C4. Analyses incorporating the available sequences estimated the substitution rate in genogroup C at 3.66¾10 "3 and 4.46¾10 "3 substitutions per site year "1 for loci 1D and 3CD, respectively, assuming a relaxed molecular-clock model for sequence evolution. Most of the 'European' strains belonged to clades C1b and C2b, which originated in 1994 [95 % confidence interval (CI), 1992.7"1995.8] and 2002 (95 % CI, 2001.6"2003, respectively. Estimates of divergence times for locus 3CD were consistent with those measured for locus 1D. Intertwining between clades representing EV-71 subgenogroups and clades corresponding to other enterovirus types (notably early coxsackievirus A prototype strains) in the 3CD phylogeny is highly indicative of ancestral recombination events. Incongruent phylogenetic patterns estimated for loci 1D and 3CD show that a single tree cannot model the epidemic history of circulating EV-71 populations. The evolutionary timescale of genogroup C estimated for both loci was measured only in decades, indicating recent dissemination.

High Frequency and Diversity of Species C Enteroviruses in Cameroon and Neighboring Countries

“…Since NPEVs are poorly sampled in sub-Saharan Africa, the extent of the circulation of this novel EV-A71 genogroup in African populations is probably underestimated. The major EV-A71 genogroups A, B, and C have been involved in several epidemics of hand-foot-and-mouth disease, severe neurological disease, and other health concerns primarily in Asia but also in Australia, Europe, and the United States (55,58,59). It has been demonstrated that diverse lineages of genogroup B and C have each silently circulated in the human population for several years before causing large outbreaks (56).…”

“…Only 4 HEV-A strains, including 2 EV-A71 strains, were identified in AFP patients. One strain of EV-A71 belonged to genogroup C, which has been associated with disease outbreaks worldwide, including Africa (54)(55)(56). Two novel genogroups were recently identified in Africa (32) and India (57), respectively.…”

Epidemiology of human enterovirus 71 infections in France, 2000–2009

“…18 The 1D gene nucleotide sequences (891 bp) were compared with all the available 1D sequences from European EV-71 strains (n = 46; GenBank, as of November 15th, 2009) and a selection of sequences from worldwide strains representing the different subgenogroups of EV-71. The 1D sequences of 27 EV-71 German and Austrian strains 19 were also included in the analysis. Multiple sequence alignments were constructed using the ClustalW v.2.0 program 20 as implemented in the Seaview v.4.0 program.…”

Emergence, Circulation, and Spatiotemporal Phylogenetic Analysis of Coxsackievirus A6- and Coxsackievirus A10-Associated Hand, Foot, and Mouth Disease Infections from 2008 to 2012 in Shenzhen, China

“…The first round of RT-snPCR based on the complete VP1 gene was performed to detect HEV-A using the primers HEVAS1495, HEVAR2C, and HEVAR2807 (19). The second round of RT-snPCR based on the complete VP1 gene was performed to detect HEV-B using the primers HEVBS1695, EV2C, and HEVBR132 (20).…”