Natural Recombination Event within the Capsid Genomic Region Leading to a Chimeric Strain of Human Enterovirus B

Abstract

Recombination between two strains is a known phenomenon for enteroviruses replicating within a single cell. We describe a recombinant strain recovered from human stools, typed as coxsackievirus B4 (CV-B4) and CV-B3 after partial sequencing of the VP1 and VP2 coding regions, respectively. The strain was neutralized by a polyclonal CV-B3-specific antiserum but not by a CV-B4-specific antiserum. The nucleotide sequence analysis of the whole structural genomic region showed the occurrence of a recombination event at position 1950 within the VP3 capsid gene, in a region coding for the 2b antigenic site previously described for CV-B3. This observation evidences for the first time the occurrence of an interserotypic recombination within the VP2-VP3-VP1 capsid region between two nonpoliovirus enterovirus strains. The neutralization pattern suggests that the major antigenic site is located within the VP2 protein.Enteroviruses are small, nonenveloped, positive singlestranded RNA viruses belonging to the family Picornaviridae. Human enteroviruses (HEV) comprise 68 serotypes, subdivided into five species on the basis of genetic properties: HEV-A to HEV-D and poliovirus (PV) (38). These viruses are responsible for a wide range of acute and chronic clinical manifestations (32).The RNA genome, 7.5 kb long, is constituted by a single open reading frame flanked by 5Ј and 3Ј untranslated regions. The coding region is translated into a single polyprotein of 2,200 amino acids and is then processed to generate four structural proteins (VP1 to VP4) and seven nonstructural proteins (2A to 2C and 3A to 3D). The four structural proteins constitute the icosahedral capsid that contains the major antigenic determinants (22) and the principal attachment sites to the cellular receptors (for a review, see reference 10).Recombination between two strains is a known phenomenon for enteroviruses replicating within a single cell. Although recombination has long been recognized as an important property of PV (9, 17), several recent publications have demonstrated that it is also extremely frequent in non-PV enteroviruses (2, 6-8, 15, 17-20, 24, 27, 28, 31, 35). Despite this high level of genetic instability, the occurrence of intra-and interserotypic recombination events in the VP2-VP3-VP1 structural coding region has been shown to be a rare phenomenon and up to now restricted to PV strains (5,14,21,40). Structural requirements of the virion shell or of receptor binding were thought to be involved in the restriction of recombination within this region (17,30,36).In this paper, we describe an interserotypic recombination event occurring in the VP3 coding region of a clinical strain of HEV-B and leading to a chimeric coxsackievirus B3 (CV-B3)/ CV-B4 type. MATERIALS AND METHODSVirus isolation and identification. The analyzed virus strain (SE-03-78616) was isolated from the KB cell line in 2003 from stools of a patient admitted for meningitis in the pediatric unit of Toulon Hospital (France). The strain was purified by the limiting dilution method in ce...

Molecular Characterization of Human Enteroviruses in the Central African Republic: Uncovering Wide Diversity and Identification of a New Human Enterovirus A71 Genogroup

“…Alternatively, these discrepancies may have resulted from recombination events that had occurred within the capsid region. Such events are believed to be infrequent, probably because of the structural constraints imposed on virions, but previous studies have shown that they can occur in both PV species (14,15,23,36,39,60,67) and non-PV HEV species (16). Further analyses are under way to determine whether the discrepancies observed between the VP1 and VP2 methods for some samples can be attributed to such uncommon recombination events.…”

Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

“…Enteroviral evolution occurs through genetic drift (Chua et al, 2001), which is primarily prominent in group B enteroviruses (Simmonds & Welch, 2006), including coxsackieviruses of group B (CVB). In addition, the occurrence of interserotypic recombination events between different coxsackievirus strains has also been reported (Bouslama et al, 2007).…”

Genome analysis of two type 6 echovirus (E6) strains recovered from sewage specimens in Greece in 2006

“…In the region 2A, LR51A5, and LR61G3 cluster with the CBV6 prototype strain (82% nucleotide identity), and in 2B with the EV82 prototype strain (84% nucleotide identity). In the region 2C-3D there is a continuous phylogenetic relationship of LR51A5 and LR61G3 with E30 strains E30-CF1319-02, E30-CF1500801-05, and E30-CF1590401 isolated in France in 2002-2005, as well as with strain SE-03-78616, belonging to CBV4, isolated in France in 2003 and found to be recombinant in the 2A genomic region with the above-mentioned E30 isolate E30-CF1319-02 [17]. The nucleotide identity between LR51A5 and LR61G3 and the E30 ''sequences'' was 83-84% in 2C, 84-86% in 3A, 87-92% in 3B, 89-91% in 3C, and 88-89% in 3D.…”

“…Recombination has been recognized as a frequent event in Poliovirus [6][7][8][9][10][11] and non-polio Enterovirus evolution [12][13][14][15][16], usually located in the noncapsid coding region. Intra-and interserotypic recombination events in the VP2-VP1 coding region have been reported to occur rarely [6,17,18]. Genetic exchanges between enteroviruses can give rise to new viral genotypes that may be extremely virulent and dangerous for public health [19].…”