In vitro screening for antiretroviral agents against simian immunodeficiency virus (SIV).
Simian immunodeficiency virus (SIV), which causes an acquired immunodeficiency syndrome in macaques, is a lentivirus that is morphologically, antigenically, genetically, and biologically similar to the human immunodeficiency virus (HIV). Because of these similarities, the SIV model represents a unique opportunity for in vitro and in vivo testing of antiretroviral agents. Since antiretroviral agents may exhibit different properties in different cells in vitro, more than one cell line may be necessary to evaluate the efficacy and modes of action of an antiretroviral agent. Initially we tested ten cell lines for their permissiveness to five SIV isolates. One B-cell line (AA-2) and one T-cell line (HuT 78) were selected to test antiretroviral agents since both were extremely permissive for SIVmac251, an isolate with a high rate of infectivity. Using this optimized in vitro testing protocol, we screened ten antiretroviral agents for their ability to inhibit SIV replication. Six of the compounds completely inhibited SIV viral antigen expression. Based on the selectivity index, 3'-azido-3'-dideoxythymidine, 3'-azido-2',3'-dideoxyuridine, and 3'-fluoro-3'-deoxythymidine appear to be the most efficacious antiretroviral agents against SIVmac251. Several different assays for determining viral antigen inhibition were conducted and the results of these assays were comparable. Our results demonstrate that the SIV in vitro model is a valuable screening tool for determining the efficacy and toxicity of new antiretroviral agents.
Tsai
C C
CC
Regional Primate Research Center, University of Washington, Seattle.
Follis
K E
KE
Yarnall
M
M
Deaver
L E
LE
Benveniste
R E
RE
Sager
P R
PR
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D008254:Macaca nemestrina; D008826:Microbial Sensitivity Tests / Q000379:methods*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; D012194:RNA-Directed DNA Polymerase