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

Aalia S. Bano, Vikas Sood, Ujjwal Neogi, Nidhi Goel, Vijesh Sreedhar Kuttiat, Ajay Wanchu, Akhil C. Banerjea

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2768-2776
Number of pages9
JournalJournal of General Virology
Volume90
Issue number11
DOIs
StatePublished - 2009
Externally publishedYes

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Open Reading Frames
HIV-1
India
Dilatation and Curettage
Genome
HIV Long Terminal Repeat
Apoptosis
vpr Genes
Sequence Analysis
Cell Cycle
Mutation
Genes
Proteins

ASJC Scopus subject areas

  • Virology
  • Medicine(all)

Cite this

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, Aalia S.; Sood, Vikas; Neogi, Ujjwal; Goel, Nidhi; Kuttiat, Vijesh Sreedhar; Wanchu, Ajay; Banerjea, Akhil C.

In: Journal of General Virology, Vol. 90, No. 11, 2009, p. 2768-2776.

Research output: Contribution to journalArticle

Bano, Aalia S. ; Sood, Vikas ; Neogi, Ujjwal ; Goel, Nidhi ; Kuttiat, Vijesh Sreedhar ; Wanchu, Ajay ; Banerjea, Akhil C. / 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. In: Journal of General Virology. 2009 ; Vol. 90, No. 11. pp. 2768-2776.
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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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AU - Bano, Aalia S.

AU - Sood, Vikas

AU - Neogi, Ujjwal

AU - Goel, Nidhi

AU - Kuttiat, Vijesh Sreedhar

AU - Wanchu, Ajay

AU - Banerjea, Akhil C.

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