       Document 0577
 DOCN  M9640577
 TI    Interferon treatment inhibits virus replication in HIV-1- and
       SIV-infected CD4+ T-cell lines by distinct mechanisms: evidence for
       decreased stability and aberrant processing of HIV-1 proteins.
 DT    9604
 AU    Agy MB; Acker RL; Sherbert CH; Katze MG; Regional Primate Research
       Center, School of Medicine, University; of Washington, Seattle 98185,
       USA.
 SO    Virology. 1995 Dec 20;214(2):379-86. Unique Identifier : AIDSLINE
       MED/96130176
 AB    We have examined the effects of interferon (IFN)-alpha/beta on HIV-1 and
       SIV replication in CD4+ T-cell lines. To enable us to examine these
       effects on a single cycle of virus replication, cells were synchronously
       infected with HIV-1 LAI or SIV mac251. Cell lines included MT4 cells
       which were responsive to IFN and, as controls, C8166 cells which failed
       to respond to interferon treatment. Similar to previous reports, we
       found that replication of both HIV-1 and SIV was markedly inhibited in
       responsive MT4 cell lines treated with IFN. No such decreases were
       observed in HIV-1-infected, IFN-treated C8166 cells. Levels of both
       intracellular and extracellular viral antigens decreased in both HIV-1-
       and SIV-infected MT4 cells treated with IFN. Whereas steady state levels
       of viral-specific RNAs dramatically declined in SIV-infected cells, no
       such decrease was observed in IFN-treated HIV-1-infected cells. In
       accordance with these data, the rate of viral protein synthesis did not
       significantly change in HIV-1-infected, IFN-treated MT-4 cells. Western
       blot analysis of extracts prepared from IFN-treated HIV-1-infected cells
       revealed a decreased accumulation of most HIV-1-specific glycoproteins
       and proteins with the exception of the pr55 gag precursor. Pulse-chase
       experiments confirmed the enhanced stability of pr55 in IFN-treated
       cells, but also unexpectedly demonstrated the accelerated and
       quantitative processing of the p26 precursor (p24 capsid [CA] plus p2)
       to the final processed p24 (CA) polypeptide. These data, taken together,
       suggest that IFN deregulated viral protein processing and caused reduced
       protein stability in HIV-1-infected cells while inhibiting an earlier
       stage of replication in SIV-infected cells.
 DE    Animal  Cell Line  CD4-Positive T-Lymphocytes/CYTOLOGY  Gene Expression
       Genes, Viral  Human  HIV Antigens/METABOLISM  HIV-1/*DRUG
       EFFECTS/PHYSIOLOGY  Interferon-alpha/*PHARMACOLOGY
       Interferon-beta/*PHARMACOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  SIV/*DRUG EFFECTS/PHYSIOLOGY  Viral Proteins/METABOLISM
       Virus Replication/*DRUG EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

