Home LiteratureArticle Details
PMID: 9114046 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

A new reporter cell line to monitor HIV infection and drug susceptibility in vitro.

Gervaix A, West D, Leoni LM, Richman DD, Wong-Staal F, Corbeil J

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
References (29)
29 references, click to expand
  1. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene.
    J Virol. 1992 Apr;66(4):2232-9 PMID: 1548759
  2. Primary structure of the Aequorea victoria green-fluorescent protein.
    Gene. 1992 Feb 15;111(2):229-33 PMID: 1347277
  3. In vitro differentiation of monocytoid THP-1 cells affects their permissiveness for HIV strains: a model system for studying the cellular basis of HIV differential tropism.
    Virology. 1993 Mar;193(1):256-67 PMID: 8438570
  4. Green fluorescent protein as a marker for gene expression.
    Science. 1994 Feb 11;263(5148):802-5 PMID: 8303295
  5. Tat-independent replication of human immunodeficiency viruses.
    J Clin Invest. 1995 Jan;95(1):328-32 PMID: 7814633
  6. The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection.
    J Virol. 1995 Feb;69(2):882-8 PMID: 7815556
  7. NF-kappa B: a lesson in family values.
    Cell. 1995 Feb 24;80(4):529-32 PMID: 7867060
  8. Chimeric green fluorescent protein as a tool for visualizing subcellular organelles in living cells.
    Curr Biol. 1995 Jun 1;5(6):635-42 PMID: 7552174
  9. HIV-1 gp120/160 expressing cells upregulate HIV-1 LTR directed gene expression in a cell line transfected with HIV-1 LTR-reporter gene constructs.
    Cell Mol Biol (Noisy-le-grand). 1995 May;41(3):445-52 PMID: 7580840
  10. Analysis of trafficking of Rev and transdominant Rev proteins in living cells using green fluorescent protein fusions: transdominant Rev blocks the export of Rev from the nucleus to the cytoplasm.
    Virology. 1995 Nov 10;213(2):439-49 PMID: 7491768
  11. HIV-induced apoptosis requires the CD4 receptor cytoplasmic tail and is accelerated by interaction of CD4 with p56lck.
    J Exp Med. 1996 Jan 1;183(1):39-48 PMID: 8551242
  12. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor.
    Science. 1996 May 10;272(5263):872-7 PMID: 8629022
  13. Identification of a major co-receptor for primary isolates of HIV-1.
    Nature. 1996 Jun 20;381(6584):661-6 PMID: 8649511
  14. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors.
    Cell. 1996 Jun 28;85(7):1149-58 PMID: 8674120
  15. Green fluorescent protein and its derivatives as versatile markers for gene expression in living Drosophila melanogaster, plant and mammalian cells.
    Gene. 1996;173(1 Spec No):83-7 PMID: 8707061
  16. The human immunodeficiency virus type 1 capsid p2 domain confers sensitivity to the cyclophilin-binding drug SDZ NIM 811.
    J Virol. 1996 Sep;70(9):5751-7 PMID: 8709190
  17. Simultaneous fluorescence-activated cell sorter analysis of two distinct transcriptional elements within a single cell using engineered green fluorescent proteins.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8508-11 PMID: 8710900
  18. Crystal structure of the Aequorea victoria green fluorescent protein.
    Science. 1996 Sep 6;273(5280):1392-5 PMID: 8703075
  19. Psoralen inactivation of influenza and herpes simplex viruses and of virus-infected cells.
    Infect Immun. 1981 Jun;32(3):1216-26 PMID: 6265375
  20. Antiviral therapy.
    Sci Am. 1987 Apr;256(4):76-85 PMID: 2436295
  21. Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity.
    J Virol. 1988 Oct;62(10):3779-88 PMID: 3047430
  22. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336-40 PMID: 2494664
  23. Treatment of HIV tissue culture infection with monoclonal antibody-ricin A chain conjugates.
    J Immunol. 1989 May 1;142(9):3070-5 PMID: 2540236
  24. Synergistic inhibition of human immunodeficiency virus type 1 and type 2 replication in vitro by castanospermine and 3'-azido-3'-deoxythymidine.
    Antimicrob Agents Chemother. 1989 Jan;33(1):53-7 PMID: 2653214
  25. Tetrazolium-based plaque assay for HIV-1 and HIV-2, and its use in the evaluation of antiviral compounds.
    J Virol Methods. 1989 Dec;26(3):319-29 PMID: 2482843
  26. A microtransfection method using the luciferase-encoding reporter gene for the assay of human immunodeficiency virus LTR promoter activity.
    Gene. 1990 Apr 16;88(2):197-205 PMID: 2189784
  27. BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine.
    Antimicrob Agents Chemother. 1991 Feb;35(2):305-8 PMID: 1708976
  28. Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist.
    Science. 1991 Dec 20;254(5039):1799-802 PMID: 1763331
  29. Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells.
    AIDS Res Hum Retroviruses. 1992 Apr;8(4):487-93 PMID: 1599755
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1997-04-29
Pages
4653-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20779
Subset
IM
Grants
NIDDK NIH HHS · DK49618 · United States
NIAID NIH HHS · U01 AI027670 · United States
NIAID NIH HHS · 1 P30 AI 36214 · United States
NCI NIH HHS · CA67394-02 · United States
NIAID NIH HHS · R37 AI029164 · United States
NIAID NIH HHS · U01 AI038858 · United States
NIAID NIH HHS · P30 AI036214 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com