HIV-1 with Predicted CXCR4 Genotype Identified in Clade C from India
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HIV-1 with Predicted CXCR4 Genotype Identified in Clade C from India Abraham Joseph Kandathil,1 Rajesh Kannangai,1 Oriapadickal Cherian Abraham,2 Susanne Alexander Pulimood,3 Mark A. Jensen4 and Gopalan Sridharan1 1 2 3 4
Department of Clinical Virology, Christian Medical College, Vellore, India Department of Internal Medicine, Christian Medical College, Vellore, India Department of Dermatology, Christian Medical College, Vellore, India Department of Genetics and Epidemiology, University of Georgia Athens, Atlanta, Georgia, USA
Abstract
Background and objective: HIV-1 uses co-receptors CCR5 and CXCR4 in addition to CD4 for viral entry into cells. CCR5 is used in the early stages of HIV-1 infection, but viruses that utilize CXCR4 for viral entry emerge in the later stages. This is not common among clade C strains, with previous data from India showing the absence of the emergence of CXCR4-using strains. Sequence analysis has demonstrated that the V3 loop plays a very important role in determining the syncytium-inducing (SI) phenotype. The V3 region of the SI variants were observed to have positively charged amino acids at positions 11 and/or 25 and also a overall higher charge. This study looked at co-receptor usage among HIV-1 strains in India from individuals who were antiretroviral therapy (ART) naı¨ ve and those not responding to ART. Methods: Amplification and sequencing of the HIV-1 env gp120 V3 region was done on 40 ART-naı¨ ve individuals, who were selected for the study based on their CD4 counts, and eight patients who had not responded to ART. The sequences were submitted to Geno2Pheno and Web PSSM. The pol gene sequences of these strains were submitted to the REGA HIV-1 subtyping tool. Results: Forty-seven strains were identified as clade C and one strain as clade A1. Geno2Pheno identified three CXCR4-using strains, and the Web PSSM clade C matrix identified two. Conclusion: We report, for the first time, CXCR4-using strains among HIV-1 clade C strains circulating in India.
Background HIV uses co-receptors in addition to CD4 receptors for viral entry into cells. The most commonly used co-receptors are the chemokine receptors CCR5 and CXCR4.[1] CCR5 co-receptors are used in the early stages of HIV-1 infection, but there is an emergence of CXCR4 usage in the later stages.[2] This occurs in about 50% of individuals infected with subtype B strains.[3] The emergence of CXCR4-using strains is not common among clade C strains.[4-5] Previous data on co-receptor usage in HIV-1 clade C strains from India have shown an absence of the emergence of CXCR4-using strains.[5] However, a recent report from Africa has shown an emergence of CXCR4-using clade C strains to the extent of 30% in infected individuals.[6] The introduction of a new class of drugs targeting CCR5 makes it
important to have data on co-receptor usage of the predominant subtype C HIV-1 strains, especially those circulating in India.[7] The envelope (env) gene of HIV-1 consi
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