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Title
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Antiviral compounds show enhanced activity in HIV-1 single cycle pseudovirus assays as compared to classical PBMC assays
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Author
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Abstract
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| HIV-1 Env pseudotyped viruses (PV) are an attractive tool for studying the antiviral activities of compounds interfering with virus entry into a target cell. To investigate whether results obtained in PV assays are relevant biologically, the antiviral activity of 6 reference compounds was compared on 5 virus isolates of different clades using three assays: (1) replicating virus in peripheral blood mononuclear cells (PBMCs), (2) PV in CD4 and CCR5- or CXCR4 co-receptor expressing Ghost cells, and (3) PV in PBMCs. A significant linear relationship was found between both single-cycle PV assays (P < 0.0001, R2 = 0.75). Moreover, both assays showed enhanced sensitivity to the antiretrovirals tested (P = 0.013 and 0.015, respectively) as compared to the PBMC assay with replication-competent virus. Most importantly, results from the latter assay could be predicted significantly from both PV assays, in which either Ghost target cells (P < 0.0001, R2 = 0.61) or PBMCs (P < 0.0001, R2 = 0.55) were used. The usefulness of the PV assay was demonstrated further by investigating the impact of the HIV-1 Env subtype on the antiviral activity of five new compounds derived from the entry inhibitor BMS806. |
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Language
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English
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Source (journal)
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Journal of virological methods. - Amsterdam
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Publication
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Amsterdam
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2008
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ISSN
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0166-0934
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DOI
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10.1016/J.JVIROMET.2007.11.009
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Volume/pages
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148
:1/2
(2008)
, p. 166-173
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ISI
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000254720500022
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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