Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from Kwazulu-Natal, South Africa: Implications for vaccine and antiretroviral control strategies
Date
2003
Authors
Gordon M.
De Oliveira T.
Bishop K.
Coovadia H.M.
Madurai L.
Engelbrecht S.
Van Rensburg E.J.
Mosam A.
Smith A.
Cassol S.
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Abstract
The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naive patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.
Description
Keywords
antiretrovirus agent, epitope, Human immunodeficiency virus vaccine, nucleoside, nucleotide, protein kinase C, proteinase, RNA directed DNA polymerase, RNA directed DNA polymerase inhibitor, adult, amino acid sequence, article, codon, controlled study, correlation analysis, cytotoxic T lymphocyte, drug binding site, drug efficacy, drug sensitivity, enzyme active site, enzyme phosphorylation, epidemic, ethnic group, female, gene disruption, gene mutation, genetic analysis, genetic polymorphism, genetic variability, glycosylation, helper cell, human, Human immunodeficiency virus 1, infection control, major clinical study, male, nucleotide sequence, phylogeny, polymorphic locus, preschool child, priority journal, protein motif, retrospective study, South Africa, virus envelope, virus resistance, virus typing, Adult, AIDS Vaccines, Amino Acid Sequence, Amino Acid Substitution, Anti-HIV Agents, Drug Resistance, Viral, Female, Genes, env, HIV Infections, HIV Protease, HIV-1, HIV-1 Reverse Transcriptase, Humans, Infant, Male, Molecular Sequence Data, Phylogeny, Sequence Analysis, DNA, South Africa, Variation (Genetics)
Citation
Journal of Virology
77
4
77
4