Effect of target cell availability on HIV-1 production in vitro

Elissa J. Schwartz, Avidan U. Neumann, Avelino V. Teixeira, Leslie A. Bruggeman, Jay Rappaport, Alan S. Perelson, Paul E. Klotman

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objective: The recovery of CD4 target cells following antiretroviral therapy may facilitate virus production and escape from antiretroviral suppression. To address this hypothesis, we directly examined whether the CD4 target cell number increases viral production in the presence of suboptimal therapy. Design: The effect of the CD4 T cell number on HIV-1 replication with a suboptimal dose of zidovudine was studied in vitro. Methods: Varying numbers of CD4 T cells were infected with HIV-1 and treated with 1 nM zidovudine. Virus production was measured by p24 antigen capture enzyme-linked immunosorbent assay. Partial sequencing of HIV-1 pol was performed to assess zidovudine-resistant mutations. Results: Wild type virus production was found to increase eightfold in cultures with 100 × 104 cells compared with cultures with 10 × 104 cells. The IC90 of zidovudine was 4 logs higher in cultures with 16 × 104 cells compared with cultures with 1 × 104 cells. No zidovudine-resistant mutations were found. Conclusion: Target cell availability may play a direct role in wild type HIV-1 resurgence following therapy.

Original languageEnglish
Pages (from-to)341-345
Number of pages5
JournalAIDS
Volume16
Issue number3
DOIs
StatePublished - 15 Feb 2002
Externally publishedYes

Funding

FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesP01DK050795
National Center for Research ResourcesR01RR006555

    Keywords

    • Antiretroviral therapy
    • Mathematical models
    • Target cell availability
    • Viral escape
    • Viral load

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