title: Antiviral compounds show enhanced activity in HIV-1 single cycle pseudovirus assays as compared to classical PBMC assays.
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.
authors.affiliation: Virology Unit, Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerpen, Belgium. lheyndrickx@itg.be <lheyndrickx@itg.be>
authors.forename: Leo
authors.initials: L
authors.lastname: Heyndrickx
authors.forename: Tine
authors.initials: T
authors.lastname: Vermoesen
authors.forename: Katleen
authors.initials: K
authors.lastname: Vereecken
authors.forename: Julia
authors.initials: J
authors.lastname: Kurth
authors.forename: Sandra
authors.initials: S
authors.lastname: Coppens
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aerts
authors.forename: Asa
authors.initials: A
authors.lastname: Ohagen
authors.forename: Yven
authors.initials: Y
authors.lastname: Van Herrewege
authors.forename: Paul
authors.initials: P
authors.lastname: Lewi
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000821:virology; D008826:Microbial Sensitivity Tests / Q000379:methods*; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D023581:HIV Fusion Inhibitors; D054299:env Gene Products, Human Immunodeficiency Virus