Abstract
Determination of HIV infectivity in vitro and its inhibition by antiretroviral drugs by monitoring reduction of production of p24 antigen is expensive and time consuming. Such assays also do not allow accurate quantitation of the number of infected cells over time. To develop a simple, rapid, and direct method for monitoring HIV infection, we generated a stable T-cell line (CEM) containing a plasmid encoding the green fluorescent protein (humanized S65T GFP) driven by the HIV-1 long terminal repeat. Clones were selected that displayed low constitutive background fluorescence, but a high level of GFP expression upon infection with HIV. HIV-1 infection induced a 100- to 1,000-fold increase in relative fluorescence of cells over 2 to 4 days as monitored by fluorescence microscopy, cytofluorimetry, and flow cytometry. Addition of inhibitors of reverse transcriptase, protease, and other targets at different multiplicities of infection permitted the accurate determination of drug susceptibility. This technique also permitted quantitation of infectivity of viral preparations by assessment of number of cells infected in the first round of infection. In conclusion, the CEM-GFP reporter cell line provides a simple, rapid, and direct method for monitoring HIV infectivity titers and antiretroviral drug susceptibility of syncytium-inducing strains.
MeSH Terms
Anti-HIV Agents/pharmacology
Cell Line/virology
Genes, Reporter
Green Fluorescent Proteins
HIV Envelope Protein gp120/isolation & purification
HIV Long Terminal Repeat
HIV Protease Inhibitors/pharmacology
HIV-1/growth & development
Luminescent Proteins/genetics
Microbial Sensitivity Tests/methods
Nevirapine
Pyridines/pharmacology
Recombinant Proteins/biosynthesis
Reverse Transcriptase Inhibitors/pharmacology
Saquinavir/pharmacology
T-Lymphocytes/cytology,virology
Zidovudine/pharmacology
Chemicals
Anti-HIV Agents
HIV Envelope Protein gp120
HIV Protease Inhibitors
Luminescent Proteins
Pyridines
Recombinant Proteins
Reverse Transcriptase Inhibitors
Green Fluorescent Proteins
Zidovudine
Nevirapine
Saquinavir
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gervaix A
Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0679, USA.
West D
Leoni L M
Richman D D
Wong-Staal F
Corbeil J
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