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Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination

Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in... Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination Kavita S. Lole 1 , Robert C. Bollinger 2 , Ramesh S. Paranjape 3 , Deepak Gadkari 1 , 3 , Smita S. Kulkarni 3 , Nicole G. Novak 2 , Roxann Ingersoll 4 , Haynes W. Sheppard 5 , and Stuart C. Ray 2 , * National Institute of Virology 1 and National AIDS Research Institute, 3 Pune, India; Division of Infectious Diseases, Department of Medicine, 2 and Center for Medical Genetics, 4 Johns Hopkins University School of Medicine, Baltimore, Maryland and Viral and Rickettsial Diseases Laboratory, California Department of Health Services, Berkeley, California 5 ABSTRACT The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env , nef , and the 3′ long terminal repeat as determined by both maximal χ 2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1 LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher ( P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Virology American Society For Microbiology

Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination

Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination

Journal of Virology , Volume 73 (1): 152 – Jan 1, 1999

Abstract

Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination Kavita S. Lole 1 , Robert C. Bollinger 2 , Ramesh S. Paranjape 3 , Deepak Gadkari 1 , 3 , Smita S. Kulkarni 3 , Nicole G. Novak 2 , Roxann Ingersoll 4 , Haynes W. Sheppard 5 , and Stuart C. Ray 2 , * National Institute of Virology 1 and National AIDS Research Institute, 3 Pune, India; Division of Infectious Diseases, Department of Medicine, 2 and Center for Medical Genetics, 4 Johns Hopkins University School of Medicine, Baltimore, Maryland and Viral and Rickettsial Diseases Laboratory, California Department of Health Services, Berkeley, California 5 ABSTRACT The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env , nef , and the 3′ long terminal repeat as determined by both maximal χ 2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1 LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher ( P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.

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Publisher
American Society For Microbiology
Copyright
Copyright © 1999 by the American society for Microbiology.
ISSN
0022-538X
eISSN
1098-5514
Publisher site
See Article on Publisher Site

Abstract

Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination Kavita S. Lole 1 , Robert C. Bollinger 2 , Ramesh S. Paranjape 3 , Deepak Gadkari 1 , 3 , Smita S. Kulkarni 3 , Nicole G. Novak 2 , Roxann Ingersoll 4 , Haynes W. Sheppard 5 , and Stuart C. Ray 2 , * National Institute of Virology 1 and National AIDS Research Institute, 3 Pune, India; Division of Infectious Diseases, Department of Medicine, 2 and Center for Medical Genetics, 4 Johns Hopkins University School of Medicine, Baltimore, Maryland and Viral and Rickettsial Diseases Laboratory, California Department of Health Services, Berkeley, California 5 ABSTRACT The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env , nef , and the 3′ long terminal repeat as determined by both maximal χ 2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1 LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher ( P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.

Journal

Journal of VirologyAmerican Society For Microbiology

Published: Jan 1, 1999

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