The CD8+ cell non-cytotoxic antiviral response affects RNA polymerase II-mediated human immunodeficiency virus transcription in infected CD4+ cells.
A CD8+ cell non-cytotoxic antiviral response (CNAR), mediated by a CD8+ cell antiviral factor (CAF), is associated with a long-term healthy state in human immunodeficiency virus (HIV) infection. CNAR/CAF reduces viral transcription without a known effect on specific viral sequences in the HIV genome. In studies to define the mechanism involved in the block in viral transcription, we now report that transcription from the HIV-LTR reporter is reduced in infected CD4+ cells upon treatment with CAF. In agreement with this observation, the amount of RNA polymerase II (RNAPII) on the HIV promoter and other viral regions was strongly diminished in HIV-infected CD4+ cells co-cultivated with CNAR-expressing CD8+ cells. These results demonstrate further that CNAR/CAF has a specific role in regulating HIV transcription and a step during the preinitiation complex assembly appears to be sensitive to CNAR/CAF.
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, Room S1280, San Francisco, CA 94143, USA.|CEITEC-Masaryk University, 62500 Brno, Czech Republic.
Dalibor
D
Blazek
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, Room S1280, San Francisco, CA 94143, USA.
Fernando
F
Teque
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, Room S1280, San Francisco, CA 94143, USA.|Amgen, Thousand Oaks, CA, USA.
Carl
C
Mackewicz
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, Room S1280, San Francisco, CA 94143, USA.
Matija
M
Peterlin
Department of Medicine, University of California San Francisco, 513 Parnassus Ave, Room S1280, San Francisco, CA 94143, USA.
Jay A
JA
Levy
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D006678:HIV / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic
D012319:RNA Polymerase II