Journal article
Coreceptor Tropism in Human Immunodeficiency Virus Type 1 Subtype D: High Prevalence of CXCR4 Tropism and Heterogeneous Composition of Viral Populations
Journal of virology, Vol.81(15), pp.7885-7893
08/2007
DOI: 10.1128/JVI.00218-07
PMCID: PMC1951291
PMID: 17507467
Abstract
In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use ranges from ∼20% in early infection to ∼50% in advanced disease. Coreceptor use by non-subtype B HIV is less well characterized. We studied coreceptor tropism of subtype A and D HIV-1 collected from 68 pregnant, antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None of 33 subtype A or 10 A/D-recombinant viruses used the CXCR4 coreceptor. In contrast, nine (36%) of 25 subtype D viruses used both CXCR4 and CCR5 coreceptors. Clonal analyses of the nine subtype D samples with dual or mixed tropism revealed heterogeneous viral populations comprised of X4-, R5-, and dual-tropic HIV-1 variants. In five of the six samples with dual-tropic strains, V3 loop sequences of dual-tropic clones were identical to those of cocirculating R5-tropic clones, indicating the presence of CXCR4 tropism determinants outside of the V3 loop. These dual-tropic variants with R5-tropic-like V3 loops, which we designated “dual-R,” use CCR5 much more efficiently than CXCR4, in contrast to dual-tropic clones with X4-tropic-like V3 loops (“dual-X”). These observations have implications for pathogenesis and treatment of subtype D-infected individuals, for the association between V3 sequence and coreceptor tropism phenotype, and for understanding potential mechanisms of evolution from exclusive CCR5 use to efficient CXCR4 use by subtype D HIV-1.
Details
- Title: Subtitle
- Coreceptor Tropism in Human Immunodeficiency Virus Type 1 Subtype D: High Prevalence of CXCR4 Tropism and Heterogeneous Composition of Viral Populations
- Creators
- Wei Huang - Monogram Biosciences, South San Francisco, CaliforniaSusan H Eshleman - Monogram Biosciences, South San Francisco, CaliforniaJonathan Toma - Monogram Biosciences, South San Francisco, CaliforniaSigne Fransen - Monogram Biosciences, South San Francisco, CaliforniaEric Stawiski - Monogram Biosciences, South San Francisco, CaliforniaEllen E Paxinos - Monogram Biosciences, South San Francisco, CaliforniaJeannette M Whitcomb - Monogram Biosciences, South San Francisco, CaliforniaAlicia M Young - Monogram Biosciences, South San Francisco, CaliforniaDeborah Donnell - Monogram Biosciences, South San Francisco, CaliforniaFrancis Mmiro - Monogram Biosciences, South San Francisco, CaliforniaPhilippa Musoke - Monogram Biosciences, South San Francisco, CaliforniaLaura A Guay - Monogram Biosciences, South San Francisco, CaliforniaJ. Brooks Jackson - Monogram Biosciences, South San Francisco, CaliforniaNeil T Parkin - Monogram Biosciences, South San Francisco, CaliforniaChristos J Petropoulos - Monogram Biosciences, South San Francisco, California
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.81(15), pp.7885-7893
- DOI
- 10.1128/JVI.00218-07
- PMID
- 17507467
- PMCID
- PMC1951291
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 08/2007
- Academic Unit
- Pathology; VPMA - Administration
- Record Identifier
- 9984046812302771
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