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ABSTRACT: Abstract While infection with HIV-1 has become a pandemic, the presence of HIV-2 is also of concern in certain regions of the world. We have characterized the gp105 region of the envelope gene of HIV-2 isolates from Western India. Phylogenetic analysis of all 18 sequences revealed that these sequences were closely related to each other as well as to published African and European HIV-2 group A sequences, with an overall genetic divergence of 10.9% (range 2-14%). Our study sequences showed close relatedness with West African HIV-2 group A (CAM group) sequences from Guinea Bissau with 89% homology. This was further confirmed by SimPlot as well as RIP analysis. Accordingly, the sequences presented here demonstrate the predominance of HIV-2 group A infection and show no evidence of HIV-2 recombination in Western India.
AIDS research and human retroviruses 02/2009; 25(1):115-21. · 2.18 Impact Factor
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ABSTRACT: The longitudinal heterologous neutralization response against two HIV-1 subtype C isolates was studied in 33 ART-naive individuals recently infected with HIV-1 subtype C from India. Seven of 33 (21%) seroconverters demonstrated a consistent response against both isolates (65-100% neutralization), whereas the remaining 26 (79%) were nonresponders. Four of the seven responders demonstrated a neutralization response (>75% neutralization) within 2-3 months of infection and in the remaining three, the response was demonstrated between 22 and 38 months after infection. In the past, HIV vaccines targeted the V3 region for the development of neutralizing antibodies. However, recent studies have shown that anti-V3 antibodies are generated after HIV-1 infection, but are not effective in neutralizing virus. In this study, the V3 sequences of HIV-1 from seven responders were analyzed and compared with those from nonresponders. The V3 region sequences from early and late responders did show certain mutations that were not found in the nonresponders; however none of these mutations could explain the neutralization responses. This suggested that HIV-1 envelope regions other than the V3 domain may be involved in generating a neutralization response. This is the first report that describes the pattern of emergence and persistence of the heterologous neutralization response in recently HIV-1 subtype C-infected individuals from India and studies its association with sequence variation in the V3 region.
AIDS research and human retroviruses 08/2008; 24(9):1159-66. · 2.18 Impact Factor
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ABSTRACT: The chemokine coreceptors play a significant role in HIV entry and pathogenesis. The V3 region of HIV envelope glycoprotein is considered as a principal determinant for viral phenotype and tropism. The present study describes lack of association between the V3 genotype and viral phenotype of 18 Indian HIV-2 isolates. The viruses were isolated, confirmed by PCR and the HIV subtypes were determined by sequencing V3 region of the env gene. The coreceptor usage and syncytium inducing (SI) capacity of isolates was determined. Our study indicated that CCR5 coreceptor usage and NSI phenotype is predominant among Indian HIV-2 isolates obtained from patients in the early stage of infection. Two of the four HIV-2 isolates obtained from the late stage patients were SI and dual tropic. Phylogenetic analysis of these isolates revealed close relatedness to the isolates from western and southern India.
Virology 07/2005; 337(1):68-75. · 3.35 Impact Factor
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ABSTRACT: Although HIV-1 subtype C is the most prevalent subtype worldwide, data on subtype C viruses are rather limited. Very little information is available on the complete HIV-1 subtype C gag sequences from India. We report full-length gag (p55) sequences from six Indian early seroconverters. The samples were collected within few weeks of seroconversion and may represent immunologically naive viruses. The comparison of p55 sequences with other Indian and non-Indian subtype C sequences as well as with nonsubtype C sequences obtained from the Los Alamos database revealed gag as a well-conserved region of the HIV genome (range: 84-95%). The phylogenetic tree indicated that the sequences compared here cluster together within clade C. Two epitopes in the p24 region of the gag gene were subtype C specific while many epitopes in the same region were also present in other clades. The data on HIV-1 subtype C full-length gag sequences would be useful in the design and evaluation of effective subtype C-based HIV vaccines.
AIDS Research and Human Retroviruses 11/2004; 20(10):1113-8. · 2.25 Impact Factor
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ABSTRACT: HIV-1 subtype C is predominant in India and globally. In the present study, we analyze HIV-1 subtype C regulatory protein Nef sequences from five recent Indian seroconverters and five long-term survivors (LTSs) for variability at crucial functional domains. Sequence analysis suggested the possibility of using regulatory gene sequences for viral subtyping and evolutionary studies apart from structural genes. In the phylogenetic tree, Indian nef sequences segregated away from other reported subtype C sequences, forming an Indian subclade within subtype C. Our studies also suggested no evidence for the association of truncated Nef with slow progression of disease, as all LTSs had intact Nef. We could identify some variations in juxtapositions to crucial functional domains, especially in seroconverter sequences, when comparing them with others. In phylogenetic analysis, specifically for the base-pair regions 411-428 and 478-525, our seroconverter sequences segregated away from those reported earlier in the literature, indicating specific evolutionary changes in these conserved regions of nef in currently circulating viruses. But the dN/dS ratio for our samples was less than one on comparing them with reported subtype C and representative sequences of different clades, strongly emphasizing the necessity of sequence conservation at different disease stages and even across clades. HLA-I binding epitope predictions for common Indian HLAs indicated that specific mutations in seroconverter Nef may alter the intensity of epitope binding, which may alter the outcome of the immune response. Hence these data would be useful in designing Nef epitopes to be included in multi-epitope HIV-1 vaccine for the Indian population and would also be of immense help in HIV-1 evolutionary studies.
Microbes and Infection 04/2004; 6(3):279-89. · 3.10 Impact Factor