Phylogenetic analysis of partial pre-membrane and envelope sequences of dengue viruses circulating in India

Phylogenetic characteristics of circulating Indian dengue viruses (DENV) were analysed using partial pre-membrane (PrM) and envelope (E) sequences. An immunodominant region was analysed for mutations, and alignment with common DENV PCR primers and probes was determined.

Published Indian PrM and E DENV sequences were analysed with hitherto unpublished PrM sequences from this study site. Alignments of DENV were checked for mutations in an immunodominant region and against the commonly used PCR primers and probes.

All four serotypes of DENV circulate in India. Genotype (G) GIII and GI of DENV-1 co-circulated in the south with significant PrM mutations before and after 2012. DENV-2 American genotype was first reported after which the Cosmopolitan genotype co-circulated with it in the southwest. The Cosmopolitan strain has been the only DENV-2 genotype circulating, although an Asian American genotype was recently reported. Significant mutations were found in the E region of DENV-2 strains. DENV-3 strains were GIII across the country. DENV-4 GI from the south and west has now spread across India. No significant mutations were found for DENV-3 or DENV-4. Indian strains showed mutations in an immunodominant region of the E gene and in the regions targeted by commonly used PCR primers and probes.

The genetic variability of Indian DENV with co-circulation of multiple genotypes suggests that genotype surveillance is crucial to determining the composition of dengue vaccines and understanding their contribution to epidemiology, virus fitness and pathogenesis. Some mutations seen in an immunodominant region of the E gene may allow these viruses to evade host immune cells. The mutations in the regions targeted by commonly used primers and probes necessitate higher degeneracy.