Chikungunya Virus (CHIKV) is a single stranded positive sense enveloped RNA virus. Re-emergence of CHIKV caused a massive
outbreak with severe clinical manifestation affecting multiple organs. The genetic diversity of CHIKV, which caused recurring
outbreaks in India, was studied. Blood samples were collected from suspected human cases of CHIKV infection in Chennai, Tamil
Nadu and three Northern districts of Kerala in Southern India during the CHIKV outbreak in 2009. A partial E2 gene segment was
amplified by RT-PCR. Among 119 samples 37 samples were positive for CHIKV by RT-PCR. Phylogenetic analysis revealed that the
isolated sequences belonged to Indian Ocean Lineage (IOL) of ECSA genotype. The mutational analysis revealed the presence of
substitutions such as S299N, T312M, A344T, S375T, V386G, W339R and S375P in the current study. In addition, a novel mutation
V386G was observed in all the sequences. Two isolates found with unique substitutions W339R and S375P are reported. The structural
analysis of the wild type and mutant proteins revealed that the structural changes are accompanied by modification in the intraprotein
interactions.