title: A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: potential impact on CTL epitopes.
abstract: The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates involving a total of 976 Vpr sequences. The polymorphisms at the individual amino acid level were analyzed. The residues 9, 33, 39, and 47 showed a single variant amino acid compared to other residues. There are several amino acids which are highly polymorphic. The residues that show ten or more variant amino acids are 15, 16, 28, 36, 37, 48, 55, 58, 59, 77, 84, 86, 89, and 93. Further, the variant amino acids noted at residues 60, 61, 34, 71 and 72 are identical. Interestingly, the frequency of the variant amino acids was found to be low for most residues. Vpr is known to contain multiple CTL epitopes like protease, reverse transcriptase, Env, and Gag proteins of HIV-1. Based on this, we have also extended our analysis of the amino acid polymorphisms to the experimentally defined and predicted CTL epitopes. The results suggest that amino acid polymorphisms may contribute to the immune escape of the virus. The available data on naturally occurring polymorphisms will be useful to assess their potential effect on the structural and functional constraints of Vpr and also on the fitness of HIV-1 for replication.
authors: Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA. alagarsamy.srinivasan@gmail.com
authors: Alagarsamy
authors: A
authors: Srinivasan
authors: Velpandi
authors: V
authors: Ayyavoo
authors: Sundarasamy
authors: S
authors: Mahalingam
authors: Aarthi
authors: A
authors: Kannan
authors: Anne
authors: A
authors: Boyd
authors: Debduti
authors: D
authors: Datta
authors: Vaniambadi S
authors: VS
authors: Kalyanaraman
authors: Anthony
authors: A
authors: Cristillo
authors: Ronald G
authors: RG
authors: Collman
authors: Nelly
authors: N
authors: Morellet
authors: Bassel E
authors: BE
authors: Sawaya
authors: Ramachandran
authors: R
authors: Murali
mesh_terms: D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016336:Gene Products, vpr / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D016334:Genes, vpr; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D016336:Gene Products, vpr