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

Journal of Virological Methods
Leo HeyndrickxGuido Vanham

Abstract

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.

References

Aug 15, 1998·Journal of Virological Methods·E BeirnaertG van der Groen
Aug 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Pin-Fang LinRichard Colonno
Feb 9, 2006·The Journal of Antimicrobial Chemotherapy·Verónica BrizVincent Soriano
Feb 24, 2006·Virology·Christoph SeibertThomas P Sakmar
Apr 14, 2006·Current Medicinal Chemistry·J Thomas Leonard, Kunal Roy
Jun 7, 2006·Antiviral Research·Dominique Schols
Aug 15, 2006·Biochemical and Biophysical Research Communications·Vidita ChoudhryDimiter S Dimitrov
Mar 6, 2007·Lancet·Jan Balzarini, Lut Van Damme

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Citations

Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alonso HerediaRobert R Redfield
Feb 21, 2009·PloS One·Eva Maria FenyöGabriella Scarlatti
Jan 1, 2017·Journal of Nanotechnology and Materials Science·Karl KhandalavalaAnnemarie Shibata

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