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.
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 alpha-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.
Bano
Aalia S
AS
Virology, National Institute of Immunology, JNU Campus, New Delhi 110067, India.
Sood
Vikas
V
Virology, National Institute of Immunology, JNU Campus, New Delhi 110067, India.
Neogi
Ujjwal
U
Virology, National Institute of Immunology, JNU Campus, New Delhi 110067, India.
Goel
Nidhi
N
Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Kuttiat
Vijesh Sreedhar
VS
Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Wanchu
Ajay
A
Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Banerjea
Akhil C
AC
Virology, National Institute of Immunology, JNU Campus, New Delhi 110067, India.
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D016000:Cluster Analysis; D005260:Female; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007194:India; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1