Evidence of extended alternate coreceptor usage by HIV-1 clade C envelope obtained from an Indian patient

Abstract

HIV-1 clade C tends to exclusively use CCR5 irrespective of disease stages. We previously reported envelopes (Envs) obtained from an Indian patient (VB105) that used CXCR4, CXCR6, CCR2b, CCR3, GPR15, and CX3CR1 as additional coreceptors besides CCR5 for entry. Here we show that the primary VB105 virus was able to replicate in peripheral blood mononuclear cells (PBMCs) in presence of inhibitors that antagonizes all the above seven coreceptors at excess doses. In addition, VB105 Envs were found to efficiently infect CCR5-defective T cells (MOLT-4) in presence of excess TAK-779, AMD3100, vMIP-1 and vMIP-2 further substantiated the usage of additional coreceptors beyond the seven coreceptors as reported earlier by VB105 Env. Interestingly, VB105 Envs showed spontaneous exposure of CD4-induced epitopes and found to be associated with increased infection of macrophages. Information on HIV-1 clade C using alternate coreceptors in primary cells to better understand their impact on pathogenesis and efficacy to future entry inhibitors.