Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines.
Promonocytic (U1) and T lymphocytic (ACH-2) cell lines chronically infected with human immunodeficiency virus type 1 (HIV-1) constitutively express low levels of virus, but expression can be induced by phorbol esters and cytokines. Whereas ACH-2 cells produce infectious virions, U1 cells produce defective, noninfectious particles. Although 3'-azido-3'-deoxythimidine (AZT) prevented acute HIV infection of susceptible cells, it did not prevent the induction of HIV expression in the infected cell lines. In contrast, interferon alpha (IFN-alpha) inhibited the release of reverse transcriptase and viral antigens into the culture supernatant after phorbol ester stimulation of both cell lines. Further, IFN-alpha suppressed the production or release (or both) of whole HIV virions, but had no effect on the amount of cell-associated viral proteins. Also, after phorbol ester stimulation of ACH-2 cells, IFN-alpha reduced the number of infectious viral particles secreted into the culture supernatant, but had no effect on the infectivity of cell-associated virus. These findings lend support to the combined use of antiviral agents that have action at both the early (AZT) and the late (IFN-alpha) stages of HIV replication.
Poli
G
G
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Orenstein
J M
JM
Kinter
A
A
Folks
T M
TM
Fauci
A S
AS
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D002460:Cell Line; D002462:Cell Membrane / Q000382:microbiology; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015151:Immunoblotting; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D008854:Microscopy, Electron; D009000:Monocytes / Q000382:microbiology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000382:microbiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014617:Vacuoles / Q000382:microbiology; D014771:Virion / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
D007370:Interferon Type I; D011994:Recombinant Proteins; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate