Evaluation of multiple parameters of HIV-1 replication cycle in testing of AIDS drugs in vitro.
Evaluation of the activities of antiretroviral agents and an immunoregulatory compound has been made using two models of HIV-1 infection and three measurements of virus expression. Acute infection of Jurkat cells or chronic/inducible infection in U1.1 cells was monitored at multiple time points after drug treatment. The 50% effective concentrations (EC50) of the HIV-1 inhibitors suramin, 3'-azido-3'-deoxythymidine (AZT), and 2',3'-dideoxycytidine, as measured by HIV-1 RNA hybridization in Jurkat cells two days after infection, were comparable to EC50 values obtained in parallel measurements of extracellular p24 levels and percent HIV-1 IF-positive cells. However, these measurements diverged: at seven days after infection the EC50 of AZT was greater than 10 microM when intracellular HIV-1 RNA was assayed, 0.2 microM by IF, and 0.03 microM by p24 assay. Human thymic humoral factor displayed no direct inductive activity in chronic HIV-1 infection in U1.1 cells, while phorbol ester and lymphocyte supernatants induced all parameters. These observations warrant care when interpreting results of only a single assay and suggest that definitive assay of HIV-1 infection requires measurements of multiple parameters of virus expression.
Volsky
D J
DJ
Molecular Virology Laboratory, St Luke's/Roosevelt Hospital Center, New York, NY.
Li
G
G
Hamblet
N
N
Volsky
B
B
Decker
R S
RS
Pellegrino
M G
MG
Potash
M J
MJ
D000998:Antiviral Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008954:Models, Biological; D010835:Phytohemagglutinins / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D013498:Suramin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013951:Thymus Hormones / Q000494:pharmacology; D014775:Virus Activation; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology; D016047:Zalcitabine / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D007155:Immunologic Factors; D010835:Phytohemagglutinins; D012367:RNA, Viral; D013951:Thymus Hormones; D015215:Zidovudine; D013498:Suramin; C014859:thymic humoral factor; D016047:Zalcitabine; D013755:Tetradecanoylphorbol Acetate