Abstract
Although the HIV-1 epidemic in India is mainly due to subtype C, other subtypes have also been reported from different parts of India. HIV-1 LTR sequence analysis from six HIV-1 infected individuals from North India was carried out to determine the nature and extent of variations. Four out of six samples formed a unique phylogenetic cluster which was close to subtype B. The other two samples (A3 and S3) turned out to be novel mosaic recombinants showing resemblance to subtypes B, B/C-India and B/C-Myanmar gene segments. All four subtype B LTR samples and the two B/C recombinants showed conserved as well as unique polymorphisms in all of the putative transcription factor binding sites (TFBS). These changes may potentially alter basal as well as Tat-mediated HIV-1 LTR promoter activation. The two recombinants possessed three copies of the NF-κB TFBS as seen with the majority of subtype C and recombinant B/C isolates reported earlier, but the other four non-recombinant B-LTRs showed only two copies of the NF-κB site. This is the first study to show a dominance of unique subtype B-LTRs and strongly suggests that this region could also be a hot spot for the formation of highly complex inter subtype B/C recombinants.
References
Bano AS, Gupta N, Sood V, Banerjea AC (2007) Vpr from HIV-1 subtypes B and C exhibit significant differences in their ability to transactivate LTR-mediated gene expression and also in their ability to promote apoptotic DNA ladder formation. AIDS 21:1832–1834
Berkhout B, Jeang KT (1992) Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol 66:139–149
Blackard JT, Renjifo BR, Mwakagile D, Montano MA, Fawzi WW, Essex M (1999) Transmission of human immunodeficiency type 1 viruses with intersubtype recombinant long terminal repeat sequences. Virology 254:220–225
Bonneau KR, Ng S, Foster H, Choi KB, Berkhout B, Rabson A, Mackewicz CE, Levy JA (2008) Derivation of infectious HIV-1 molecular clones with LTR mutations: sensitivity to the CD8 (+) cell noncytotoxic HIV response. Virology 373:30–38
Harrich D, Garcia J, Wu F, Mitsuyasu R, Gonzalez J, Gaynor R (1989) Role of Sp1-binding domains in in vivo transcription regulation of the human immunodeficiency virus type 1 long terminal repeat. J Virol 63:2585–2591
Harrich D, Hsu C, Race E, Gaynor RB (1994) Differential growth kinetics are exhibited by human immunodeficiency virus type 1 TAR mutants. J Virol 68:5899–5910
Husain S, Goila R, Shahi S, Banerjea AC (1998) First report of a healthy Indian heterozygous for Δ 32 mutant of HIV-1 co-receptor-CCR5 gene. Gene 207:141–147
Jones JA, Kadonga JT, Luciw PA, Tijan R (1986) Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science 232:755–759
Lakhashe S, Tripathy S, Paranjape R, Bhattacharya J (2008) Evidence of a novel B/C recombinant exhibiting unique breakpoints of near full-length HIV Type 1 genome from Northeastern India. AIDS Res Hum Retroviruses 24:229–234
Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160
Mansky LM (1998) Retrovirus mutation rates and their role in genetic variation. J Gen Virol 79:1337–1345
Mehta R, Sundaravaradan V, Ahmad N (2008) Mutations generated in human immunodeficiency virus type 1 long terminal repeat during vertical transmission correlate with viral gene expression. Virology 375:170–181
Millow KH, Greenough TC, Bretttler DB, Schindler M, Wildum S, Sullivan JL, Kirchhoff F (2003) Alterations in HIV-1 LTR promoter activity during AIDS progression. Virology 317:109–118
Monatano M, Novitsky VA, Blackard JT, Cho NL, Katzenstein DA, Essex M (1997) Divergent transcriptional regulation among expanding human immunodeficiency virus type 1 subtypes. J Virol 71:8657–8665
Nabel G, Baltimore D (1987) An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 326:711–713
Pereira LA, Bentley K, Peeters A, Churchill MJ, Deacon NJ (2000) A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter. Nucleic Acids Res 28:663–668
Rodriguez MA, Shen C, Ratner D, Paranjape RS, Kulkarni SS, Chatterjee R, Gupta P (2007) Genetic and functional characterization of the LTR of HIV-1 subtypes A and C circulating in India. AIDS Res Hum Retroviruses 23:1428–1433
Romanchikova N, Ivanova V, Scheller C, Jankevics E, Jassoy C, Serfling E (2003) NFAT transcription factors control HIV-1 expression through a binding site downstream of TAR region. Immunobiology 208:361–365
Salminen MO, Carr JK, Burke DS, McCutchan FE (1995) Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning. AIDS Res Hum Retroviruses 11:1423–1425
Sood V, Ranjan R, Banerjea AC (2008) Functional analysis of HIV-1 subtypes B & C HIV-1 Tat exons and RGD/QGD motifs with respect to Tat-mediated transactivation and apoptosis. AIDS 22:1683–1685
Takebe Y, Motomura K, Masashi T, Lwin HH, Zwa M, Kusagwa S (2003) High prevalence of diverse forms of HIV-1 intersubtype recombinants in Central Myanmar: geographical hot spot of extensive recombination. AIDS 17:2077–2087
Yang R, Xia X, Kusagawa S, Zhang C, Ben K, Takebe Y (2002) On going generation of multiple forms of HIV-1 intersubtype recombinants in the Yunnan Province of China. AIDS 16:1401–1407
Acknowledgments
This work was supported by a grant from the Department of Biotechnology, Government of India, to the corresponding author (A.C.B) and to the National Institute of Immunology, New Delhi, India. We thank our Director, Dr. Avadesh Surolia, for support and encouragement. Support received from PGIMER, Chandigarh, is gratefully acknowledged.
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Ujjwal Neogi and Vikas Sood contributed equally to this work.
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Neogi, U., Sood, V., Goel, N. et al. Novel HIV-1 long terminal repeat (LTR) sequences of subtype B and mosaic intersubtype B/C recombinants in North India. Arch Virol 153, 1961–1966 (2008). https://doi.org/10.1007/s00705-008-0210-y
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DOI: https://doi.org/10.1007/s00705-008-0210-y