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 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.
Heyndrickx
Leo
L
Virology Unit, Department of Microbiology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerpen, Belgium. lheyndrickx@itg.be <lheyndrickx@itg.be>
Vermoesen
Tine
T
Vereecken
Katleen
K
Kurth
Julia
J
Coppens
Sandra
S
Aerts
Laetitia
L
Ohagen
Asa
A
Van Herrewege
Yven
Y
Lewi
Paul
P
Vanham
Guido
G
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
D023581:HIV Fusion Inhibitors; D054299:env Gene Products, Human Immunodeficiency Virus