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A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: Potential impact on CTL epitopes

Alagarsamy Srinivasan1*, Velpandi Ayyavoo2*, Sundarasamy Mahalingam3, Aarthi Kannan14, Anne Boyd1, Debduti Datta3, Vaniambadi S Kalyanaraman5, Anthony Cristillo5, Ronald G Collman6, Nelly Morellet7, Bassel E Sawaya8 and Ramachandran Murali9

Author Affiliations

1 Thomas Jefferson University, Department of Microbiology and Immunology, Jefferson Alumni Hall Rm 461, 1020 Locust Street, Philadelphia, PA 19107, USA

2 University of Pittsburgh, Department of Infectious Diseases & Microbiology, Parran Hall Rm 439, 130 DeSoto Street, Pittsburgh, PA 15261, USA

3 Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India

4 Wellesley College, 21 Wellesley College Rd Unit 7430, Wellesley, MA 02481, USA

5 Advanced Bioscience Laboratories, Inc., 5510 Nicholson Lane, Kensington, MD 20895, USA

6 University of Pennsylvania School of Medicine, 522 Johnson Pavilion, 36th and Hamilton Walk, Philadelphia PA 19104, USA

7 Unite de Pharmacologie Chimique et Genetique, INSERM, Avenue de l'Observatoire, Paris Cedex 06, France

8 Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19122, USA

9 University of Pennsylvania School of Medicine, Dept of Pathology and Laboratory Medicine, 243 John Morgan, Philadelphia PA 19104, USA

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Virology Journal 2008, 5:99  doi:10.1186/1743-422X-5-99

Published: 23 August 2008

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.