The type I human T-cell leukemia virus (HTLV-I) Rex trans-activator binds directly to the HTLV-I Rex and the type 1 human immunodeficiency virus Rev RNA response elements.
The Rex protein of the type I human T-cell leukemia virus (HTLV-I) is essential for the replication of this pathogenic retrovirus and, surprisingly, can also replace the function of the structurally distinct Rev protein of the type 1 human immunodeficiency virus (HIV-1). Rex action requires a 255-nucleotide viral RNA stem-loop structure termed the Rex RNA response element (RexRE) located in the 3' retroviral long terminal repeat. Rex function leads to the induced cytoplasmic expression of the incompletely spliced family of viral mRNAs that uniquely encode the HTLV-I structural and enzymatic proteins (Gag, Pol, and Env). Our studies now demonstrate that Rex acts by binding directly to the RexRE in a sequence-specific manner. These effects of Rex require the presence of a 10-nucleotide subregion of the RexRE that is essential for Rex function in vivo. Dominant-negative mutants of Rex also bind to the RexRE with high affinity, while a recessive-negative Rex mutant altered within its arginine-rich, positively charged domain fails to engage the RexRE. Analogously, both the wild-type and dominant-negative Rex proteins specifically bind to the structurally distinct HIV-1 Rev response element, a finding that likely underlies the respective stimulatory and inhibitory effects of these HTLV-I proteins in the heterologous HIV-1 system. However, consistent with their lack of amino acid homology, the binding sites for Rex and Rev within the HIV-1 Rev response element are distinct.
Bogerd
H P
HP
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.
Huckaby
G L
GL
Ahmed
Y F
YF
Hanly
S M
SM
Greene
W C
WC
D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D004926:Escherichia coli; D015694:Gene Products, rev / Q000235:genetics*; D016370:Gene Products, rex / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D009154:Mutation; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D054321:rev Gene Products, Human Immunodeficiency Virus
D002352:Carrier Proteins; D015694:Gene Products, rev; D016370:Gene Products, rex; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus