ArticleJournal of virology2009
Selection of a simian-human immunodeficiency virus strain resistant to a vaginal microbicide in macaques.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Multifaceted mechanisms of HIV inhibition and resistance to CCR5 inhibitors PSC-RANTES and Maraviroc.Antimicrobial agents and chemotherapy · 2013Article
- Closing the door to human immunodeficiency virus.Protein & cell · 2013Review
- A multi-targeted drug candidate with dual anti-HIV and anti-HSV activity.PLoS pathogens · 2013Article
- HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the envelope glycoprotein gp120.Journal of virology · 2013Article
- Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR) RNA.PLoS pathogens · 2011Article
- Article
- Resistance to the CCR5 inhibitor 5P12-RANTES requires a difficult evolution from CCR5 to CXCR4 coreceptor use.PloS one · 2011Article
- SHIV-162P3 infection of rhesus macaques given maraviroc gel vaginally does not involve resistant viruses.PloS one · 2011Article
- Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor.The Journal of infectious diseases · 2010Article
- "Resistance" to PSC-RANTES revisited: two mutations in human immunodeficiency virus type 1 HIV-1 SF162 or simian-human immunodeficiency virus SHIV SF162-p3 do not confer resistance.Journal of virology · 2010Article
- HIV-1 Entry, Inhibitors, and Resistance.Viruses · 2010Article
- Generation of the pathogenic R5-tropic simian/human immunodeficiency virus SHIVAD8 by serial passaging in rhesus macaques.Journal of virology · 2010Article
- siRNA-based topical microbicides targeting sexually transmitted infections.Current opinion in molecular therapeutics · 2010Review
- Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials.Nature reviews. Immunology · 2009Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
PSC-RANTES binds to CCR5, inhibits human immunodeficiency virus type 1 (HIV-1) entry, and has been shown as a vaginal microbicide to protect rhesus macaques from a simian-human immunodeficiency virus chimera (SHIV(SF162-p3)) infection in a dose-dependent manner. In this study, env gene sequences from SHIV(SF162-p3)-infected rhesus macaques treated with PSC-RANTES were analyzed for possible drug escape variants. Two specific mutations located in the V3 region of gp120 (K315R) and C-helical domain of gp41 (N640D) were identified in a macaque (m584) pretreated with a 100 microM dose of PSC-RANTES. These two env mutations were found throughout infection (through week 77) but were found at only low frequencies in the inoculating SHIV(SF162-p3) stock and in the other SHIV(SF162-p3)-infected macaques. HIV-1 env genes from macaque m584 (env(m584)) and from inoculating SHIV(SF162-p3) (env(p3)) were cloned into an HIV-1 backbone. Increases in 50% inhibitory concentrations to PSC-RANTES with env(m584) were modest (sevenfold) and most pronounced in cells expressing rhesus macaque CCR5 as compared to human CCR5. Nonetheless, virus harboring env(m584), unlike inoculating virus env(p3), could replicate even at the highest tissue culture PSC-RANTES concentrations (100 nM). Dual-virus competitions revealed a dramatic increase in fitness of chimeric virus containing env(m584) (K315R/N640D) over that containing env(p3), but again, only in rhesus CCR5-expressing cells. This study is the first to describe the immediate selection and infection of a drug-resistant SHIV variant in the face of a protective vaginal microbicide, PSC-RANTES. This rhesus CCR5-specific/PSC- RANTES resistance selection is particularly alarming given the relative homogeneity of the SHIV(SF162-p3) stock compared to the potential exposure to a heterogeneous HIV-1 population in human transmission.
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