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

David J. Volsky, Gongrong Li, Natasha Hamblet, Barbara Volsky, R. Scott Decker, Michael G. Pellegrino, Mary Jane Potash

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 μM when intracellular HIV-1 RNA was assayed, 0.2 μM by IF, and 0.03 μM 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.

Original languageEnglish
Pages (from-to)335-347
Number of pages13
JournalAntiviral Research
Volume17
Issue number4
DOIs
StatePublished - Apr 1992
Externally publishedYes

Keywords

  • Chronic infection
  • Human immunodeficiency virus
  • Multiple parameter evaluation
  • Reverse transcriptase inhibitor

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