A new contained human immunodeficiency virus type 1 host cell system for evaluation of antiviral activities of interferons and other agents in vitro.
HIV-host infection systems in vitro are important in the pre-clinical assessment of anti-retroviral drug activity. The present report describes the development of a new HIV-host model comprised of an epithelial cell line of HeLa lineage (HeLa-1), transfected with expression vectors bearing tat and rev (TART) genes of HIV-1 as well as the CD4 receptor gene, and HIV-1(delta Tat/Rev), a biologically contained strain of HIV-1 deleted in tat and rev. Measurement of infectivity, by syncytium formation and reverse transcriptase assay, revealed that HeLa-1 is infected with HIV-1(deltaTat/Rev). This virus failed to productively infect the TART-deficient CD4-positive HeLa cells, confirming its contained, non-infectious nature. The HeLa-1/HIV-1deltaTat/Rev system was used to measure the anti-retroviral activity of a human leukocyte-derived interferon (IFN-alphan3) preparation, several nucleoside analogs, and protease inhibitors. The HeLa-1/ HIV-1(deltaTat/Rev model provides a biologically contained system for the study of the HIV pathogenesis and the relative and combined therapeutic effects of anti-retroviral agents in vitro.
Moussazadeh
M
M
Interferon Sciences Inc., New Brunswick, NJ 08901, USA.
Hua
J
J
Sidhu
M K
MK
Zhao
X X
XX
Fitzgibbon
J E
JE
Liao
M J
MJ
Rashidbaigi
A
A
D019380:Anti-HIV Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015870:Gene Expression; D015694:Gene Products, rev / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D019888:Nelfinavir / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019438:Ritonavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015694:Gene Products, rev; D015696:Gene Products, tat; D017320:HIV Protease Inhibitors; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D015215:Zidovudine; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir