Autor(es): Sreekumar E, Issac Aneesh, Nair Sajith, Hariharan Ramkumar, Janki M B, Arathy D S, Regu R, Mathew Thomas, Anoop M, Niyas K P, Pillai M R

Resumo: Chikungunya virus (CHIKV), a positive-str-ed alphavirus, causes epidemic febrile infections characterized by severe - prolonged arthralgia. In the present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120; 2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala, South India, were analyzed for genetic variations by sequencing the 11798 bp whole genome of the virus. A total of 37 novel mutations were identified - they were predominant in the 2007 - 2008 isolates among the six isolates studied. The previously identified E1 A226V critical mutation, which enhances mosquito adaptability, was present in the 2007 - 2008 samples. An important observation was the presence of two coding region substitutions, leading to nsP2 L539S - E2 K252Q change. These were identified in three isolates (2007 RGCB80 - RGCB120; 2008 RGCB355) by full-genome analysis, - also in 13 of the 31 additional samples (42%), obtained from various parts of the state, by sequencing the corresponding genomic regions. These mutations showed 100% co-occurrence in all these samples. In phylogenetic analysis, formation of a new genetic clade by these isolates within the East, Central - South African (ECSA) genotypes was observed. Homology modeling followed by mapping revealed that at least 20 of the identified mutations fall into functionally significant domains of the viral proteins - are predicted to affect protein structure. Eighteen of the identified mutations in structural proteins, including the E2 K252Q change, are predicted to disrupt T-cell epitope immunogenicity. Our study reveals that CHIK virus with novel genetic changes were present in the severe Chikungunya outbreaks in 2007 - 2008 in South India.

Palavras-Chave: Alphavirus; Positive-stranded RNA; Lineage; Virulence; Mutations; Epitope

Imprenta: Virus Genes, v. 40, n. 1, p. 14-27, 2010

Identificador do Objeto Digital: 10.1007/s11262-009-0411-9

Descritores: Chikungunya virus - Cell ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemic ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de Publicação: 2010