Inhibition of cellular activation of retroviral replication by CD8+ T cells derived from non-human primates.
To test the hypothesis that CD8+ T cells inhibit viral replication at the level of cellular activation, an Epstein-Barr virus (EBV)-transformed cell line (FEc1) from a simian immunodeficiency virus (SIV)-seropositive sooty mangabey monkey was transfected with a human CD4 gene and shown to be replication-competent for HIV-1, HIV-2 and SIV. Utilizing a dual-chamber culture system, it was found that inhibition of viral replication can be mediated by a soluble factor. The FEc1 cell line was transiently transfected with an LTR-driven CAT reporter gene. It was found that autologous CD8+ T cells markedly inhibited CAT activity. Furthermore, co-transfection of the FEc1 cell line with an LTR-driven tat plasmid and LTR-CAT was able to quantitatively mitigate the suppressive effect. Thus, this inhibition appears to be directed at cellular mechanisms of viral transcription. Control transfections with an LTR-driven CAT plasmid with a mutation at the NFkB binding site yielded no CAT activity, suggesting that most viral replication as measured by CAT activity is dependent, to a large extent, upon cellularly derived NFkB binding proteins.
Powell
J D
JD
Department of Pathology and Laboratory Medicine, Winship Cancer Centre, Emory University School of Medicine, Atlanta, GA 30322.
Bednarik
D P
DP
Folks
T M
TM
Jehuda-Cohen
T
T
Villinger
F
F
Sell
K W
KW
Ansari
A A
AA
D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D016665:Cercocebus atys; D015696:Gene Products, tat / Q000235:genetics; D016322:HIV Enhancer / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development; D015498:HIV-2 / Q000235:genetics / Q000254:growth & development; D004854:Herpesvirus 4, Human; D007165:Immunosuppression Therapy; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014162:Transfection; D014775:Virus Activation / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus