Regulation of human retroviral latency by the NF-kappa B/I kappa B family: inhibition of human immunodeficiency virus replication by I kappa B through a Rev-dependent mechanism.
The cellular transcription factor NF-kappa B stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional initiation, but its role in the retroviral life cycle has not been fully defined. In this report, we show that I kappa B alpha acts as a cellular inhibitor of human retroviral replication through a discrete mechanism, independent of its effect on HIV transcription. I kappa B alpha inhibited HIV replication and gp160 expression by negatively regulating Rev function, most likely acting through a cellular factor involved in Rev transactivation. A similar effect was observed with human T leukemia virus I, in which I kappa B alpha inhibited Rex function. In contrast, no effect was observed on the replication of a DNA virus, adenovirus type 5. The NF-kappa B/I kappa B regulatory pathway therefore modulates human retroviral replication by regulating a program of cellular gene expression required for several steps in the viral life cycle, including not only viral transcription but also RNA export. This interaction between cellular and viral gene products suggests that NF-kappa B plays a broader role in the regulation of human retroviral replication, providing a previously unrecognized link between two important regulators of HIV gene expression and common NF-kappa B-dependent programs of gene expression used by human retroviruses.
Wu
B Y
BY
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650.
Woffendin
C
C
Duckett
C S
CS
Ohno
T
T
Nabel
G J
GJ
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000235:genetics; D015694:Gene Products, rev / Q000502:physiology*; D016370:Gene Products, rex / Q000502:physiology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction; D051841:Transcription Factor RelB; D014157:Transcription Factors; D017735:Virus Latency; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D015686:Gene Products, env; D015694:Gene Products, rev; D016370:Gene Products, rex; D019302:HIV Envelope Protein gp160; D016328:NF-kappa B; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D054321:rev Gene Products, Human Immunodeficiency Virus; D051841:Transcription Factor RelB