1. Characterization of V3 sequence heterogeneity in subtype C human immunodeficiency virus type 1 isolates from Malawi: underrepresentation of X4 variants.
- Author
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Ping LH, Nelson JA, Hoffman IF, Schock J, Lamers SL, Goodman M, Vernazza P, Kazembe P, Maida M, Zimba D, Goodenow MM, Eron JJ Jr, Fiscus SA, Cohen MS, and Swanstrom R
- Subjects
- Base Sequence, DNA, Viral, Evolution, Molecular, Genetic Heterogeneity, HIV Envelope Protein gp120 metabolism, HIV-1 growth & development, HIV-1 isolation & purification, HIV-1 metabolism, Humans, Malawi, Molecular Sequence Data, Nucleic Acid Heteroduplexes, Peptide Fragments metabolism, RNA, Viral blood, Receptors, CCR5 metabolism, Receptors, CXCR4 metabolism, Genetic Variation, HIV Envelope Protein gp120 genetics, HIV Seropositivity virology, HIV-1 genetics, Peptide Fragments genetics
- Abstract
We have examined the nature of V3 sequence variability among subtype C human immunodeficiency virus type 1 (HIV-1) sequences from plasma-derived viral RNA present in infected men from Malawi. Sequence variability was assessed by direct sequence analysis of the V3 reverse transcription-PCR products, examination of virus populations by a subtype C V3-specific heteroduplex tracking assay (V3-HTA), and selected sequence analysis of molecular clones derived from the PCR products. Sequence variability in V3 among the subtype C viruses was not associated with the presence of basic amino acid substitutions. This observation is in contrast to that for subtype B HIV-1, where sequence variability is associated with such substitutions, and these substitutions are determinants of altered coreceptor usage. Evolutionary variants in subtype C V3 sequences, as defined by the V3-HTA, were not correlated with the CD4 level in the infected person, while such a correlation was found with subtype B V3 sequences. Viruses were isolated from a subset of the subjects; all isolates used CCR5 and not CXCR4 as a coreceptor, and none was able to grow in MT-2 cells, a hallmark of the syncytium-inducing phenotype that is correlated with CXCR4 usage. The overall sequence variability of the subtype C V3 region was no greater than that of the conserved regions of gp120. This limited sequence variability was also a feature of subtype B V3 sequences that do not carry the basic amino acid substitutions associated with altered coreceptor usage. Our results indicate that altered coreceptor usage is rare in subtype C HIV-1 isolates in sub-Saharan Africa and that sequence variability is not a feature of the V3 region of env in the absence of altered coreceptor usage.
- Published
- 1999
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