A trans-dominant negative HIV type 1 Rev with intact domains of NLS/NOS and NES.
The nuclear diffusion inhibitory signal (NIS) is a 15-amino acid peptide motif (10-24; EDLLKAVRLIKFLYQ) in the N-terminus of the HIV-1 Rev protein. NIS appears to be involved in maintaining the proper nucleocytoplasmic trafficking and intracellular stability of HIV-1 Rev. Deletion in NIS leads to Rev functional inactivity, and these data led to further investigation of its possible inhibitory effects on Rev function. An HIV-1 proviral rescue assay was utilized to evaluate Rev function. The association between wild-type Rev molecules, or wild-type Rev with Revd23, an NIS mutant, plus Rev-responsive element (RRE) interactions in cultured cells were also evaluated. Revd23 showed a potent trans-dominant negative phenotype, while multimerization with wild-type Rev and Revd23-RRE binding in cells were found to reveal no significant changes from wildtype. These results suggest that the potential trans-dominance mechanism of Revd23 may differ from that of a Rev construct, RevM10, with mutations in the C-terminus nuclear export signal (NES). As such, these data will be useful in the rational design of novel antiretroviral approaches targeting HIV-1 Rev.
Fang
Jianhua
J
Department of Medicine, Division of Infectious Diseases, The Dorrance H. Hamilton Laboratories, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Kubota
Satoshi
S
Pomerantz
Roger J
RJ
D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002466:Cell Nucleolus / Q000378:metabolism*; D004058:Diffusion; D015694:Gene Products, rev / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000502:physiology; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020218:Response Elements; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D016655:HIV Core Protein p24; D054321:rev Gene Products, Human Immunodeficiency Virus