UNIGE document Scientific Article
previous document  unige:26049  next document
add to browser collection
Title

PSC-RANTES blocks R5 human immunodeficiency virus infection of Langerhans cells isolated from individuals with a variety of CCR5 diplotypes

Authors
Kawamura, Tatsuyoshi
Bruce, Shannon E
Abraha, Awet
Sugaya, Makoto
Arts, Eric J
Zimmerman, Peter A
show hidden authors show all authors [1 - 9]
Published in Journal of Virology. 2004, vol. 78, no. 14, p. 7602-9
Abstract Topical microbicides that effectively block interactions between CCR5(+) immature Langerhans cells (LC) residing within genital epithelia and R5 human immunodeficiency virus (HIV) may decrease sexual transmission of HIV. Here, we investigated the ability of synthetic RANTES analogues (AOP-, NNY-, and PSC-RANTES) to block R5 HIV infection of human immature LC by using a skin explant model. In initial experiments using activated peripheral blood mononuclear cells, each analogue compound demonstrated marked antiviral activity against two R5 HIV isolates. Next, we found that 20-min preincubation of skin explants with each RANTES analogue blocked R5 HIV infection of LC in a dose-dependent manner (1 to 100 nM) and that PSC-RANTES was the most potent of these compounds. Similarly, preincubation of LC with each analogue was able to block LC-mediated infection of cocultured CD4(+) T cells. Competition experiments between primary R5 and X4 HIV isolates showed blocking of R5 HIV by PSC-RANTES and no evidence of increased propagation of X4 HIV, data that are consistent with the specificity of PSC-RANTES for CCR5 and the CCR5(+) CXCR4(-) phenotype of immature LC. Finally, when CCR5 genetic polymorphism data were integrated with results from the in vitro LC infection studies, PSC-RANTES was found to be equally effective in inhibiting R5 HIV in LC isolated from individuals with CCR5 diplotypes known to be associated with low, intermediate, and high cell surface levels of CCR5. In summary, PSC-RANTES is a potent inhibitor of R5 HIV infection in immature LC, suggesting that it may be useful as a topical microbicide to block sexual transmission of HIV.
Keywords Anti-HIV Agents/pharmacologyCD4-Positive T-Lymphocytes/virologyChemokine CCL5/analogs & derivatives/pharmacologyCoculture TechniquesCulture Techniques/methodsGenotypeHIV Infections/virologyHIV-1/drug effects/metabolism/pathogenicityHumansLangerhans Cells/virologyPolymorphismGeneticReceptorsCCR5/genetics/metabolismSkin/cytology/virology
Identifiers
PMID: 15220435
Full text
Article (Published version) (299 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group HIV (835)
Citation
(ISO format)
KAWAMURA, Tatsuyoshi et al. PSC-RANTES blocks R5 human immunodeficiency virus infection of Langerhans cells isolated from individuals with a variety of CCR5 diplotypes. In: Journal of Virology, 2004, vol. 78, n° 14, p. 7602-9. https://archive-ouverte.unige.ch/unige:26049

190 hits

0 download

Update

Deposited on : 2013-01-30

Export document
Format :
Citation style :