Inhibition of HIV replication by dominant negative mutants of Sam68, a functional homolog of HIV-1 Rev

被引:131
作者
Reddy, TR
Xu, WD
Mau, JKL
Goodwin, CD
Suhasini, M
Tang, HL
Frimpong, K
Rose, DW
Wong-Staal, F [1 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Whittier Diabetes Program, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Vet Med Res Fdn, La Jolla, CA 92093 USA
关键词
D O I
10.1038/9479
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The HIV-1 Rev protein facilitates the nuclear export of mRNA containing the Rev response element (RRE) through binding to the export receptor CRM-1. Here we show that a cellular nuclear protein, Sam68 (Src-associated protein in mitosis), specifically interacts with RRE and can partially substitute for as well as synergize with Rev in RRE-mediated gene expression and virus replication. Differential sensitivity to leptomycin B, an inhibitor of CRM-1, indicates that the export pathways mediated by Rev and Sam68 are distinct. C-terminally deleted mutants of Sam68 inhibited the transactivation of RRE-mediated expression by both wild-type Sam68 and Rev. They were retained in the cytoplasm and impeded the nuclear localization of Rev in coexpressed cells. These mutants also inhibited wild-type HIV-1 replication to the same extent as the RevM 10 mutant, and may be useful as anti-viral agents in the treatment of AIDS.
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收藏
页码:635 / 642
页数:8
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