Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene.
Interferon inhibits expression of human immunodeficiency virus type-1 (HIV-1) through unknown mechanisms. A gene inducible by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) was isolated by screening of a human complementary DNA library for proteins binding to the Rev-responsive element (RRE) of HIV-1. The product of this gene, RBP9-27, was shown to bind RNA in vitro and to inhibit HIV-1 expression after transfection into human cells. RBP9-27 primarily inhibited Rev-dependent posttranscriptional steps of viral gene expression. Thus, RBP9-27 is a cellular factor that antagonizes Rev function. These results suggest an interferon-induced antiviral mechanism operating through the induction of RNA binding proteins such as RBP9-27. Elucidation of RBP9-27 function may lead to a better understanding of the mechanism of interferon action during HIV-1 infection.
Constantoulakis
P
P
Human Retrovirus Section, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.
Campbell
M
M
Felber
B K
BK
Nasioulas
G
G
Afonina
E
E
Pavlakis
G N
GN
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D015967:Gene Expression Regulation, Viral; D015752:Genes, env; D015757:Genes, rev; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid
C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C080084:RBP9-27 protein, human; D016601:RNA-Binding Proteins; D007372:Interferons