Genetic analysis of Indian HIV-1 nef: subtyping, variability and implications

Jere, Abhay; Tripathy, Srikanth; Agnihotri, Kalpana; Jadhav, Sushama; Paranjape, Ramesh

doi:10.1016/j.micinf.2003.11.012

Cited by 17 publications

(10 citation statements)

References 34 publications

(45 reference statements)

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“…Simplot analysis revealed more than 90% homology of study subtype C sequences with consensus C. Phylogenetic analysis of the study sequences revealed random subclustering of the 73 study subtype C sequences along with Indian subtype C and non-Indian subtype C sequences, thus emphasizing HIV-1 subtype C pol gene diversity. This was unlike previous studies reporting segregation of Indian subtype C gag, env (gp120, gp41), and nef sequences, [18][19][20][21] probably due to the relatively conserved nature of the HIV-1 subtype C pol gene.…”

Section: Discussioncontrasting

confidence: 99%

Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Peripheral Blood Mononuclear Cell Proviral DNA among Antiretroviral Treatment-Naive and Treatment-Experienced Patients from Pune, India

Sen

Tripathy

Chimanpure

et al. 2007

AIDS Research and Human Retroviruses

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The prevalence of HIV drug resistance (HIVDR) mutations in the HIV protease (PR) and reverse transcriptase (RT) genes was estimated from peripheral blood mononuclear cells (PBMCs) in a study population of 25 antiretroviral (ARV) therapy-naive and 50 ARV-experienced chronically infected patients from Pune city, Maharashtra State, western India. Of the 75 study HIV-1 sequences, 73 belonged to subtype C and 2 to subtype A1. On phylogenetic analysis, the study subtype C sequences sub clustered randomly with different Indian and non-Indian subtype C sequences, emphasizing the HIV-1 subtype C pol gene diversity. The heterosexual route was the most common route of transmission (74.67%). There were no observable HIVDR mutations in ARV-naive patients. The ARV-experienced patients had a history of exposure to nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor combinations. At least one HIVDR mutation in RT was observed in 29 (80.55%) of ARV-experienced patients with evidence of failing therapy. M184V was the most common observed HIVDR mutation. No PR major mutations were observed among ARV-experienced patients. A higher prevalence of proviral HIVDR mutations in PBMCs was associated with irregular adherence to therapy (p < 0.05) and HIV-1 RNA levels > 1000 copies/ml (p < 0.001).

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Section: Discussioncontrasting

confidence: 99%

Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Peripheral Blood Mononuclear Cell Proviral DNA among Antiretroviral Treatment-Naive and Treatment-Experienced Patients from Pune, India

Sen

Tripathy

Chimanpure

et al. 2007

AIDS Research and Human Retroviruses

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“…This idea is supported by the partial loss of other biological activities upon mutation of these residues. 9 The domain ATN (aa position 49-51) in consensus C and vaccine candidates is replaced by DTT in most of our sequences as also observed by Jere et al 23 However, a plausible implication for and biological significance of these mutations are not known. An endocytic (E/D)xxxLL signal (dileucine motif at aa E165 and E166) was conserved in all of our sequences (Fig.…”

Section: Heterogeneity In the Nef Gene And Its Plausible Implicationssupporting

confidence: 68%

“…[15][16][17] Although researchers from diversified geographic areas have delineated the evolving sequences of the nef gene in Western and African isolates, [18][19][20][21] very little is known about the genomic heterogeneity in the nef gene sequences of Indian isolates of HIV-1 subtype C (only two studies on a handful of isolates have been carried out on Indian strains to date). 22,23 The present study was, therefore, intended to reveal full-length nef gene sequences for as many as 43 clinical isolates of HIV-1 from the eastern and northern parts of India. Besides use in genotyping and evolutionary studies, the findings may also serve as baseline data for identifying putative CTL and neutralizing antibody epitopes in nef for future designing of a multiepitope vaccine effective against Indian strains of HIV.…”

Section: Introductionmentioning

confidence: 99%

Genomic Diversity in the RegulatorynefGene Sequences in Indian Isolates of HIV Type 1: Emergence of a Distinct Subclade and Predicted Implications

Kumar

Jain

Pasha

et al. 2006

AIDS Research and Human Retroviruses

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The regulatory functional nef gene is known to mediate a cascade of events during pathogenesis in HIV infection. Variability in the nef gene sequences of HIV-1 A and B subtypes has been well documented. Reasonable data are also available on the pattern of genomic changes in the nef gene of African strains of HIV-1 subtype C, but very little is known about heterogeneity in the nef gene of Indian strains of HIV-1 subtype C, which accounts for 90% of the estimated 5.2 million cases of HIV infection in India. This is a huge number and, therefore, it is important to reveal the extent of sequence variability in the nef gene of HIV-1 subtypes circulating in different parts of India. We carried out full-length nef gene (approximately 620 bp) sequencing on a large number of clinical isolates of HIV-1 circulating in different geographic regions of India. Comparative and phylogenetic analysis revealed 88% (38/43) of cases was HIV-1 subtype C; four cases were diagnosed as subtype A and only one as subtype B. Although most of the crucial functional motifs of the nef gene were conserved, we did observe a few important variations in juxtapositions to functional domains. Interestingly, analyzed nef sequences showed an evolving pattern of segregation away from those reported from other parts of the world, to form a distinct Indian subclade. Deduced amino acid (aa) sequences used to predict HLA binding epitopes for consensus nef gene sequences of Indian strains of HIV-1 revealed two HLA subtype binding domains, GAFDLSFFL (at aa 83) and LTFGWCFKL (at aa 136), in high frequency. The findings from the present study may encourage use of nef gene in molecular diagnostics/genotyping, keeping track of the evolutionary trend and pinpointing the emergence of recombinant strains, and in the future, designing a multiepitope HIV vaccine suitable for the Indian population.

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“…We recently reported subtype B-and C-specific differences in Vpr-mediated cell cycle progression (Bano et al, 2007a) and in their ability to activate the HIV-1 LTR promoter and cause apoptosis (Bano et al, 2007b). Although genetic variations among several HIV-1 genes such as nef, env and ltr have been reported from different regions of India (Jere et al, 2004;Rodriguez et al, 2007;Bhanja et al, 2007), we provide data on the genetic and functional analysis of Vpr genes from the Punjab/Haryana region of north India, which show the involvement of other subtypes in infections in this region.…”

Section: Introductionmentioning

confidence: 99%

Genetic and functional characterization of human immunodeficiency virus type 1 VprC variants from north India: presence of unique recombinants with mosaic genomes from B, C and D subtypes within the open reading frame of Vpr

Bano

Sood

Neogi

et al. 2009

Journal of General Virology

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The human immunodeficiency virus type 1 (HIV-1) epidemic in India is predominantly caused by genetic subtype C, though other minor subtypes have also been reported. One of the major accessory proteins of HIV-1, namely Vpr, is known to influence key steps in viral replication, cell cycle progression, promoter activation, apoptosis and pathogenesis. Therefore, we carried out a genetic and functional analysis of the Vpr variants from eight HIV-1-infected individuals from north India. The sequence analyses revealed that six of eight samples clustered with ancestral subtype C. Remarkably, five of these showed a conserved and region-specific L64P mutation, located in the predicted third α-helix. This change adversely affected their ability to activate the HIV-1 long terminal repeat promoter without compromising their ability to cause apoptosis. Bootscan, phylogenetic and SimPlot analysis of the remaining two samples (VprS2 and A6) revealed very interesting mosaic genomes derived from B, C and D subtypes. The N-terminal half of the VprS2 gene consisted of genomic segments derived from subtypes B/D, C and D but the C-terminal half was derived predominantly from subtype C. Interestingly the N-terminal half of sample A6 also showed similar B/D, C and D inter-subtype recombinant structure but the C-terminal half was entirely derived from the consensus B subtype. Multiple breakpoints in a short stretch of 291 nt encoding the Vpr gene strongly suggest that this region is a potential hot-spot for the formation of inter-subtype recombinants and also highlight the importance of the rapidly evolving HIV-1 epidemic in the north Indian region due to multiple genetic subtypes.

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Genetic analysis of Indian HIV-1 nef: subtyping, variability and implications

Cited by 17 publications

References 34 publications

Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Peripheral Blood Mononuclear Cell Proviral DNA among Antiretroviral Treatment-Naive and Treatment-Experienced Patients from Pune, India

Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Peripheral Blood Mononuclear Cell Proviral DNA among Antiretroviral Treatment-Naive and Treatment-Experienced Patients from Pune, India

Genomic Diversity in the RegulatorynefGene Sequences in Indian Isolates of HIV Type 1: Emergence of a Distinct Subclade and Predicted Implications

Genetic and functional characterization of human immunodeficiency virus type 1 VprC variants from north India: presence of unique recombinants with mosaic genomes from B, C and D subtypes within the open reading frame of Vpr

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