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Genetic and Functional Characterization of HIV-1 VprC Variants from North India: Presence of Unique Recombinants with Mosaic Genomes from B, C and D Subtypes within the ORF of Vpr

¹ National Institute of Immunology;
² NII;
³ PGIMER

⁴ E-mail: akhil{at}nii.res.in

HIV-1 epidemic in India is predominantly caused by genetic subtype-C, though other minor subtypes have also been reported. One of the major accessory proteins of HIV-1, namely Vpr, is known to influence key steps in viral replication, cell cycle progression, promoter activation, apoptosis and pathogenesis. Therefore we carried out a genetic and functional analysis of the Vpr variants from 8 HIV-1 infected individuals from North India. The sequence analyses revealed that 6 out of 8 samples clustered with ancestral C. Remarkably, 5 of them showed conserved and region-specific L64P mutation, located in the predicted 3rd alpha-helix. This change adversely affected their ability to activate HIV-1 LTR promoter without compromising their ability to cause apoptosis. Bootscan, phylogenetic and simplot analysis of the remaining two samples (VprS2 and A6) revealed very interesting mosaic genomes derived from B, C and D subtypes. The N-terminal half of VprS2 gene consisted of genomic segments derived from subtypes B/D, C, and D but the C-terminal half was derived predominantly from subtype C. Interestingly the N-terminal half of sample A6 also showed similar B/D, C and D inter-subtype recombinant structure but the C-terminal half was entirely derived from the consensus B subtype. Multiple breakpoints in a short stretch of 291 nt encoding Vpr gene strongly suggest that this region is a potential hot spot for the formation of inter-subtype recombinants and also highlight the importance of the rapidly evolving HIV-1 epidemic in the North Indian region due to multiple genetic subtypes.

Received 17 February 2009; accepted 13 July 2009.