Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau.
Ovine IFN-tau is a newly described protein related to IFN-alpha that is responsible for maternal recognition of pregnancy in sheep. It has been shown to exhibit potent antiviral and antiproliferative activity. To determine its antiviral activity against feline immunodeficiency virus (FIV) and HIV, the activity of the RNA-dependent DNA polymerase, reverse transcriptase, was assayed in FIV- and HIV-infected feline and human PBL treated with IFN-tau. Significant dose-dependent inhibition of reverse transcriptase activity by IFN-tau was detected by day 6 of culture and was maintained through the peak of virus replication. In addition, production of the FIV core protein, p25, was blocked by IFN-tau. Both the amino- and carboxyl-terminal regions of IFN-tau, as identified by synthetic peptides, appear to be involved in its antiretroviral activity. Comparison of the anti-HIV activities of IFN-tau and recombinant human IFN-alpha2 (rHuIFN-alpha2) indicated that while rHuIFN-alpha2 was toxic to cells at 10,000 U/ml, IFN-tau antiretroviral activity was not associated with a decrease in either cell viability or immunologic reactivity. Thus, IFN-tau displayed potent anti-FIV and anti-HIV activity without the cytotoxicity associated with high concentrations of rHuIFN-alpha2.
Pontzer
C H
CH
Department of Microbiology, University of Maryland, College Park 20742, USA.
Yamamoto
J K
JK
Bazer
F W
FW
Ott
T L
TL
Johnson
H M
HM
D000818:Animals; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002415:Cats; D002478:Cells, Cultured; D004285:Dogs; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects*; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011994:Recombinant Proteins; D012756:Sheep; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C020947:interferon tau; D007371:Interferon-gamma; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase