Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Rex function and the interaction of cellular proteins with the cis-acting repressive sequences (CRS) within HTLV-II RNA (Meeting abstract).
International Association for Comparative Research on Leukemia and Related Diseases, 16th Symposium. July 11-16, 1993, Montreal, Quebec, Canada, A39, 1993.. Unique Identifier : AIDSLINE ICDB/94698641 Black AC; Ruland CT; Bakker A; Luo J; Rosenblatt JD; Div. of Hematology/Oncology, Dept. of Medicine, UCLA Sch. of; Medicine, Los Angeles, CA 90024-1678
Abstract:
The shift from viral regulatory to structural gene expression in human T-cell leukemia viruses (HTLVs) and human immunodeficiency viruses (HIVs) is mediated by Rex and Rev, respectively. Both Rev and Rex interact with cognate RNA response elements to overcome the inhibitory effects of cis-acting repressive elements located elsewhere in the genome. We previously showed that HTLV-II responsive element (RxRE) in 5' long terminal repeat (LTR) RNA. HTLV-II Rex acts through the RxRE to increase cytoplasmic levels of gag/pol mRNA by overcoming the block to nuclear export conferred by cis-acting repressive sequences (CRS) between nucleotides (nt) +208 to +317 in the 5' LTR. We demonstrate by electrophoretic mobility-shift assay that cellular proteins in a HeLa nuclear extract bind specifically to transcripts containing the HTLV-II CRS. Using UV cross-linking of gel-retarded bands, we identified a major protein species of approximately 60 kD that specifically binds to the CRS. Cross competition binding assays and UV cross-linking suggest that this 60 kD protein may interact with another 40 kD protein that binds to downstream RNA from nt +332 to +436. HTLV-II CRS function in a transient transfection assay correlates with 40 kD protein interaction with HTLV-II CRS RNA. Both the 60 kD and 40 kD cellular proteins also bind to HIV-1 RNAs that contain previously described CRS elements, suggesting similar underlying mechanisms of action. These data suggest that Rex and Rev may interact with the CRS binding proteins to facilitate expression of viral mRNA containing the CRS. The nature of these cellular proteins is under investigation in our laboratory.
Keywords: Amino Acid Sequence Gene Products, gag/GENETICS Gene Products, pol/GENETICS Gene Products, rev/*GENETICS Gene Products, rex/*GENETICS Hela Cells Human HIV Long Terminal Repeat/GENETICS HIV-1/GENETICS HTLV-II/*GENETICS RNA, Messenger/METABOLISM RNA, Viral/GENETICS/METABOLISM Transfection ABSTRACT 940830
M9480800
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