Abstract
BackgroundUnderstanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine using in silico methods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences.ResultsR5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months) compared to R5-tropic strains (20.5 months).ConclusionsHigh prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.
Highlights
Understanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations
The simplest method used for delineating HIV-1 tropism is known as the ‘charge rule’ [8], which relies on the charge of amino acids at positions 11 or 25 within the V3 loop when aligned against a consensus
While X4-tropic HIV-1 subtype C strains have been widely reported from Africa [14,15,16], the presence of CXCR4 as a co-receptor to facilitate entry into the host cell is uncommon among Indian subtype C strains [17,18]
Summary
Understanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. A number of tools are available online to predict the co-receptor usage on the basis of the V3 sequence Such tools include among others, (i) Geno2Pheno which predicts whether the corresponding virus is capable of using CXCR4 as a coreceptor (R5/X4 or X4 variants) or not (R5 variants) [10], (ii) the distant segments (ds)Kernel which include relative positional information of segments in a string of symbols which detects R5-, X4- and R5X4-tropic strains[11], and (iii) WebPSSM using CPSSM, a genotypic predictor based on position-specific scoring matrices (PSSM) which detects R5- or X4- tropic strains specially designed and validated for HIV-1 subtype C [12]. R5-tropic viruses constitute by far the predominant strains in India recent reports indicate the occasional presence of HIV-1 subtype C X4-tropic strains [19,20,21]
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