Echovirus 6 (E6) and echovirus 11 (E11) are common causes of meningitis and other human diseases; they are among the most frequently isolated enteroviruses worldwide. In the present work we have studied genetic variability over the entire VP1 gene of selected isolates representing a wide geographical and temporal range. Fifty new sequences from North Africa were included, together with previously published sequences from different countries. The sequence diversity between strains of the same type was high: 22 and 30 % for E6 and E11, respectively. Phylogenetic analysis revealed five genogroups within each type, the genetic diversity within a genogroup generally being ,20 %. Some genogroups were further subdivided into genotypes, most containing isolates that had circulated over a wide geographical (several countries from different continents) and temporal (up to two decades) range. Several genotypes were also shown to co-circulate in a region during the same period of time. These features differ from other enteroviruses that divide into temporal or geographical clusters. This study reports new sequences from North Africa, updates the molecular epidemiology of E6 and E11, and proposes a new genogroup in each type.
INTRODUCTIONHuman enteroviruses (HEVs) are small non-enveloped viruses with a worldwide distribution. Laboratory diagnosis of related infections currently is based on virus detection by isolation in cell culture or by direct PCR amplification from clinical samples. HEV types are identified by seroneutralization or partial sequencing of the VP1 region (Caro et al., 2001;Norder et al., 2001;Oberste et al., 1999a Oberste et al., , b, 2000Palacios et al., 2002). Similar to other RNA viruses, HEVs have a high capacity to evolve genetically. Genotypes are identified based on the genetic variability and phylogenetic relationships among isolates. The circulation of these genotypes throughout the world and over time has been studied to increase our understanding of the dynamics of their transmission, to evaluate their endemicity and to explain the extent of epidemics when they occur. Beyond type identification, sequencing of the VP1 region has also proved to be a reliable method for such molecular epidemiological studies.Echovirus 6 (E6) and echovirus 11 (E11) are among the most commonly isolated HEVs worldwide, and are frequently associated with outbreaks and sporadic cases of aseptic meningitis, as well as with several diseases ranging from mild non-specific illness to encephalitis, paralysis, myocarditis and severe systemic infections in neonates (Abe et al., 2000;Ashwell et al., 1996;Atkinson et al., 1998;Bahri et al., 2005;Belguith et al., 2007a;Boyd et al., 1987;Cabrerizo et al., 2008;Chomel et al., 2003;Druyts-Voets, 1997;El-Sageyer et al., 1998;Joo et al., 2005;Khetsuriani et al., 2006;Mao et al., 2010;Mirand et al., 2008;Miwa & Sawatari, 1994;Somekh et al., 2001;Ventura et al., 2001). However, despite their important impact on human health, studies of the molecular epidemiology of E6 and E11 remain li...