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- Bano, AS, et al.
(författare)
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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
- 2009
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 90:Pt 11, s. 2768-2776
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
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| 3. |
- Neogi, U, et al.
(författare)
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Genetic analysis of HIV-1 Circulating Recombinant Form 02_AG, B and C subtype-specific envelope sequences from Northern India and their predicted co-receptor usage
- 2009
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Ingår i: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 6, s. 28-
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 epidemic in India is largely driven by subtype C but other subtypes or recombinants have also been reported from several states of India. This is mainly due to the co-circulation of other genetic subtypes that potentially can recombine to generate recombinant/mosaic genomes. In this study, we report detail genetic characterization of HIV-1 envelope sequences from North India (Delhi and neighboring regions). Six of 13 were related to subtype C, one B and the rest six showed relatedness with CRF02_AG strain. The subtype C possessed the highly conserved GPGQ motif but subtype B possessed the GPGR motif in the V3 loop as observed earlier. While most of the sequences suggested CCR5 co-receptor usage, one subtype C sample clearly indicated CXCR4 usage. A successful mother to child transmission was established in two pairs. Thus, co-circulation of multiple subtypes (B and C) and the recombinant CRF02_AG strains in North India suggests a rapidly evolving scenario of HIV-1 epidemic in this region with impact on vaccine formulation. Since this is the first report of CRF02_AG envelope from India, it will be important to monitor the spread of this strain and its impact on HIV-1 transmission in India.
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