HIV-1 clade C env clones obtained from an Indian patient exhibiting expanded coreceptor tropism are presented with naturally occurring unusual amino acid substitutions in V3 loop

HIV-1 subtype C is predominantly circulating in India and has been reported to be strictly CCR5 tropic irrespective of disease stages. In the present study, we examined env clones obtained from a late stage Indian patient with a history of multiple sexual partners and opportunistic infections for coreceptor usage and V3 loop sequence. The env clones were found to exploit several coreceptors in addition to CCR5 in a cell-associated and cell-free manner. Analysis of V3 loop sequence revealed that the NARI-VB105 env clones were presented with unique amino acid substitutions with GPGR motif, atypical of clade C envelope. Further genetic analysis showed the V3 sequences albeit belonging to subtype C; however clustered distinctly to that of other clade C envelopes originated in different geographical regions. Modelling data revealed that NARI-VB105 V3 loop contained several basic residues giving rise a high net positive charge of +8 to these envelopes.