Evaluation of multiple parameters of HIV-1 replication cycle in testing of AIDS drugs in vitro.

Abstract

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.

• Authors: D J Volsky, G Li, N Hamblet, B Volsky, R S Decker, M G Pellegrino, M J Potash
• Journal: Antiviral research (Antiviral Res) Vol. 17 Issue 4 Pg. 335-47 (Apr 1992) ISSN: 0166-3542 [Print] Netherlands
• PMID: 1322647 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• HIV Core Protein p24
• Immunologic Factors
• Phytohemagglutinins
• RNA, Viral
• Thymus Hormones
• Zidovudine
• Suramin
• thymic humoral factor
• Zalcitabine
• Tetradecanoylphorbol Acetate

Topics

• Antiviral Agents (pharmacology)
• Drug Evaluation, Preclinical (methods)
• HIV Core Protein p24 (analysis)
• HIV-1 (drug effects, growth & development)
• Humans
• Immunologic Factors (pharmacology)
• Models, Biological
• Phytohemagglutinins (metabolism)
• RNA, Viral (analysis)
• Suramin (pharmacology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Thymus Hormones (pharmacology)
• Virus Activation
• Virus Replication (drug effects, physiology)
• Zalcitabine (pharmacology)
• Zidovudine (pharmacology)