Antiviral compounds show enhanced activity in HIV-1 single cycle pseudovirus assays as compared to classical PBMC assays

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 o...

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Bibliographic Details
Published in:Journal of virological methods 2008-03, Vol.148 (1), p.166-173
Main Authors: Heyndrickx, Leo, Vermoesen, Tine, Vereecken, Katleen, Kurth, Julia, Coppens, Sandra, Aerts, Laetitia, Ohagen, Asa, Van Herrewege, Yven, Lewi, Paul, Vanham, Guido
Format: Article
Language:English
Subjects:
Antiviral activity
Biological and medical sciences
Cell Line
Cells, Cultured
Entry inhibitors
env Gene Products, Human Immunodeficiency Virus - genetics
Fundamental and applied biological sciences. Psychology
HIV Fusion Inhibitors - pharmacology
HIV-1
HIV-1 - drug effects
Human immunodeficiency virus 1
Humans
Inhibitory Concentration 50
Leukocytes, Mononuclear - virology
Microbial Sensitivity Tests - methods
Microbiology
Molecular Sequence Data
Pseudovirus
Sequence Analysis, DNA
Techniques used in virology
Virology
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Summary: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, R 2 = 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, R 2 = 0.61) or PBMCs ( P < 0.0001, R 2 = 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.
ISSN:0166-0934
1879-0984
DOI:10.1016/j.jviromet.2007.11.009