Genetic characterization of 2006–2008 isolates of Chikungunya virus from Kerala, South India, by whole genome sequence analysis

Abstract

Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic febrile infections characterized by severe and 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 and they were predominant in the 2007 and 2008 isolates among the six isolates studied. The previously identified E1 A226V critical mutation, which enhances mosquito adaptability, was present in the 2007 and 2008 samples. An important observation was the presence of two coding region substitutions, leading to nsP2 L539S and E2 K252Q change. These were identified in three isolates (2007 RGCB80 and RGCB120; 2008 RGCB355) by full-genome analysis, and 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 and 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 and 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 and 2008 in South India.

Molecular characterization of Chikungunya virus isolates from clinical samples and adult Aedes albopictus mosquitoes emerged from larvae from Kerala, South India

“…An E2 I211T mutation was found to strongly enhance Ae.albopictus infectivity of CHIKV strains with the E1 A226V change [31]. Both the mutations were present in the isolates in this study and also in the recent Indian isolates [10,12,14] (Figure 5). Interestingly, the novel mutation in E2 (L210Q) that was detected exclusively in these 2009 CHIKV strains was adjacent to the E2-211 position.…”

“…Kerala, in South India, was one among the worst affected states [11-14]. Abundance of Ae.albopictus in many parts of the state was implicated for the rapid spread of the infection [11].…”

Induction of Cytopathogenicity in Human Glioblastoma Cells by Chikungunya Virus

“…Characterization of the RGCB355/KL08 CHIKV strain (GenBank Accession No. GQ428214) by whole genome sequencing has been previously described [22]. The virus was isolated by three serial passages in Vero cells prior to use for infecting U-87 MG cells.…”

Inhibition of Chikungunya Virus Replication by Harringtonine, a Novel Antiviral That Suppresses Viral Protein Expression

“…CHIKV is an enveloped virus with a singlestranded, positive-sense RNA genome. The CHIKV genome is approximately 11 kb long and consists of two open reading frames which encode the viral nonstructural proteins (nsP1, nsP2, nsP3, and nsP4) as well as the viral structural proteins, which include the capsid (C) and envelope proteins (E1, E2, E3, and 6k) (22,23). The envelope proteins E1 and E2 form glycoprotein spikes on the viral particle surface and facilitate the initial binding of the viral particle to susceptible host cells.…”