Acute flaccid paralysis (AFP) associated with coxsackievirus type B3 (CV-B3) of the species Enterovirus B is an emerging concern worldwide. Although CV-B3-associated AFP in India has been demonstrated previously, the genomic characterization of these strains is unreported. Here, CV-B3 strains detected on the basis of the partial VP1 gene in 10 AFP cases and five asymptomatic contacts identified from different regions of south-western India during 2009–2010 through the Polio Surveillance Project were considered for complete genome sequencing and characterization. Phylogenetic analysis of complete VP1 gene sequences of global CV-B3 strains classified Indian CV-B3 strains into genogroup GVI, along with strains from Uzbekistan and Bangladesh, and into a new genogroup, GVII. Genomic divergence between genogroups of the study strains was 14.4 % with significantly lower divergence (1.8 %) within GVI (n = 12) than that within GVII (8.5 %) (n = 3). The strains from both AFP cases and asymptomatic contacts, identified mainly in coastal Karnataka and Kerala, belonged to the dominant genogroup GVI, while the GVII strains were recovered from AFP cases in north interior Karnataka. All study strains carried inter-genotypic recombination with the structural region similar to reference CV-B3 strains, and 5′ non-coding regions and non-structural regions closer to other enterovirus B types. Domain II structures of 5′ non-coding regions, described to modulate virus replication, were predicted to have varied structural folds in the two genogroups and were attributed to differing recombination patterns. The results indicate two distinct genomic compositions of CV-B3 strains circulating in India and suggest the need for concurrent analysis of viral and host factors to further understand the varied manifestations of their infections.
DholeT. N., AyyagariA., ChowdharyR., ShakyaA. K., ShrivastavN., DattaT., PrakashV.2009; Non-polio enteroviruses in acute flaccid paralysis children of India: vital assessment before polio eradication. J Paediatr Child Health 45:409–413 [View Article][PubMed]
DunnJ. J., BradrickS. S., ChapmanN. M., TracyS. M., RomeroJ. R.2003; The stem loop II within the 5′ nontranslated region of clinical coxsackievirus B3 genomes determines cardiovirulence phenotype in a murine model. J Infect Dis 187:1552–1561 [View Article][PubMed]
ICMR2006; Ethical guidelines for biomedical research on human participants. Indian Council of Medical Research, New Delhi. Available from: http://icmr.nic.in/ethical_guidelines.pdf (accessed 10 August 2015).
KaplanM. H., KleinS. W., McPheeJ., HarperR. G.1983; Group B coxsackievirus infections in infants younger than three months of age: a serious childhood illness. Rev Infect Dis 5:1019–1032 [View Article][PubMed]
KyriakopoulouZ., PliakaV., AmoutziasG. D., MarkoulatosP.2015; Recombination among human non-polio enteroviruses: implications for epidemiology and evolution. Virus Genes 50:177–188 [View Article][PubMed]
LaxmivandanaR., YergolkarP., GopalkrishnaV., ChitambarS. D.2013; Characterization of the non-polio enterovirus infections associated with acute flaccid paralysis in South-Western India. PLoS One 8:e61650 [View Article][PubMed]
LoleK. S., BollingerR. C., ParanjapeR. S., GadkariD., KulkarniS. S., NovakN. G., IngersollR., SheppardH. W., RayS. C.1999; Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160[PubMed]
LukashevA. N., LashkevichV. A., IvanovaO. E., KorolevaG. A., HinkkanenA. E., IlonenJ.2005; Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions. J Gen Virol 86:3281–3290 [View Article][PubMed]
ObersteM. S., MaherK., KilpatrickD. R., FlemisterM. R., BrownB. A., PallanschM. A.1999; Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 37:1288–1293[PubMed]
OrtnerB., HuangC. W., SchmidD., MutzI., WewalkaG., AllerbergerF., YangJ. Y., HuemerH. P.2009; Epidemiology of enterovirus types causing neurological disease in Austria 1999–2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes. J Med Virol 81:317–324 [View Article][PubMed]
PrusaJ., MissakJ., KittrellJ., EvansJ. J., TapprichW. E.2014; Major alteration in coxsackievirus B3 genomic RNA structure distinguishes a virulent strain from an avirulent strain. Nucleic Acids Res 42:10112–10121 [View Article][PubMed]
RacanielloV. R.2007; Picornaviridae: the viruses and their replication. In Fields Virology, 5th edn. pp 796–839Edited byKnipeD. M., HowleyP. M. Philadelphia, PA: Lippincott Williams & Wilkins;
WangX., ZhuC., BaoW., ZhaoK., NiuJ., YuX. F., ZhangW.2012; Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China. PLoS One 7:e32405 [View Article][PubMed]