Inhibitory effects of IFN-gamma on HIV-1 replication in latently infected cells.
The progress in the use of HAART for the treatment of HIV-infected individuals has been limited by the development of viral resistance and the maintenance of viral latency. New therapeutic strategies geared toward improvement in the host's immune response are now being considered. We found that IFN-gamma induces CIITA through the JAK-STAT pathway and inhibits HIV-1 replication in latently infected cells. Its effect appears to be mediated through the reciprocal action of Tat and CIITA. With this beneficial effect, IFN-gamma and its inducers can be considered as an adjunct to the currently available therapy. We also addressed the safety of using simvastatin, an HMG-CoA reductase inhibitor, to treat dyslipidemia often associated with the use of protease inhibitors. Simvastatin did not show any unfavorable effects on HIV replication, thus could be used safely unless there are any drug interactions when administered.
Sarol
Lilen C
LC
Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Imai
Kenichi
K
Asamitsu
Kaori
K
Tetsuka
Toshifumi
T
Barzaga
Nina G
NG
Okamoto
Takashi
T
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015696:Gene Products, tat / Q000378:metabolism; D017930:Genes, Reporter; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor; D019821:Simvastatin / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; C503684:CCNT1 protein, human; D056906:Cyclin T; D016213:Cyclins; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D019821:Simvastatin