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Pre-incubation of cell-free HIV-1 group M isolates with non-nucleoside reverse transcriptase inhibitors blocks subsequent viral replication in co-cultures of dendritic cells and T cells

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dc.contributor.author Njai, H. F. en_US
dc.contributor.author Lewi, P. J. en_US
dc.contributor.author Janssen, C. G. M. en_US
dc.contributor.author Garcia, S. en_US
dc.contributor.author Fransen, K. en_US
dc.contributor.author Kestens, L. en_US
dc.contributor.author Vanham, G. en_US
dc.contributor.author Janssen, P. A. J. en_US
dc.date.accessioned 2007-12-06T14:47:43Z
dc.date.available 2007-12-06T14:47:43Z
dc.date.issued 2005 en_US
dc.identifier.issn 1359-6535 en_US
dc.identifier.other ITG-M1B en_US
dc.identifier.other ITG-M4B en_US
dc.identifier.other ITG-M5A en_US
dc.identifier.other ITG-M6A en_US
dc.identifier.other ITG-M7A en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-IMMUN en_US
dc.identifier.other U-VIROL en_US
dc.identifier.other JIF en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.uri http://hdl.handle.net/10390/1882
dc.description This is the author’s version of a work accepted for publication by International Medical Press. Changes resulting from the publishing process, including peer review, editing and formatting, might not be reflected in this document. A definitive version was published in Antiviral Therapy, [10, 2], 2005, © 2005 International Medical Press en_US
dc.description.abstract In order to study the inhibitory effect of various reverse transcriptase inhibitors (RTIs) on cell-free HIV, we adapted a recently described in vitro system, based on co-cultures of dendritic cells and resting CD4 T cells, modelling early target cells during sexual transmission. The compounds tested included the second-generation non-nucleoside RTI (NNRTI) TMC-120 (R147681, dapivirine) and TMC-125 (R165335, travertine), as well as the reference nucleoside RTI AZT (zidovudine), the nucleotide RTI PMPA (tenofovir) and the NNRTI UC-781. The virus strains included the reference strain HIV-1Ba-L and six primary isolates, representative of the HIV-1 group M pandemic. They all display the non-syncytium-inducing and CCR5 receptor-using (NSI/R5) phenotype, important in transmission. Cell-free virus was immobilized on a poly-L-lysine (PLL)-treated microwell plate and incubated with compound for 1 h. Afterwards, the compound was thoroughly washed away; target cells were added and cultured for 2 weeks, followed by an extended culture with highly susceptible mitogen-activated T cells. Viral production in the cultures was measured on supernatant with HIV antigen ELISA. Negative results were confirmed by showing absence of proviral DNA in the cells. TMC-120 and TMC-125 inhibited replication of HIV-1Ba-L with average EC50 values of 38 nM and 117 nM, respectively, whereas the EC50 of UC-781 was 517 nM. Complete suppression of virus and provirus was observed at compound concentrations of 100, 300 and 1000 nM, respectively. Inhibition of all primary isolates followed the same pattern as HIV-1Ba-L. In contrast, pre-treating the virus with the nucleotide RTI PMPA and AZT failed to inhibit infection even at a concentration of 100000 nM. These data clearly suggest that NNRTIs inactivate RT enzymatic activity of different viral clades (predominant in the epidemic) and might be proposed for further testing as a sterilizing microbicide worldwide. en_US
dc.language English en_US
dc.publisher International Medical Press en_US
dc.subject Viral diseases en_US
dc.subject HIV-1 group M en_US
dc.subject Virus replication en_US
dc.subject Dendritic cells en_US
dc.subject T-cells en_US
dc.subject Reverse transcriptase inhibitors en_US
dc.subject Non-nucleoside en_US
dc.subject Microbicides en_US
dc.title Pre-incubation of cell-free HIV-1 group M isolates with non-nucleoside reverse transcriptase inhibitors blocks subsequent viral replication in co-cultures of dendritic cells and T cells en_US
dc.type Article en_US
dc.citation.issue 2 en_US
dc.citation.jtitle Antiviral Therapy en_US
dc.citation.volume 10 en_US
dc.citation.pages 255-262 en_US
dc.publisher.place London en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/15865220
dc.citation.jabbreviation Antiviral Ther en_US


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