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PMID: 2072452 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mutational definition of the human immunodeficiency virus type 1 Rev activation domain.

Journal of virology ·Vol. 65 ·No. 8 ·1991-08-00 ·Pages 4248-54

Malim MH, McCarn DF, Tiley LS, Cullen BR

Abstract

Replication of human immunodeficiency virus type 1 requires the functional expression of the virally encoded Rev protein. The binding of this nuclear trans activator to its viral target sequence, the Rev-response element, induces the cytoplasmic expression of unspliced viral mRNAs. Mutation of the activation domain of Rev generates inactive proteins with normal RNA binding capabilities that inhibit wild-type Rev function in a trans-dominant manner. Here, we report that the activation domain comprises a minimum of nine amino acids, four of which are critically spaced leucines. The preservation of this essential sequence in other primate and nonprimate lentivirus Rev proteins indicates that this leucine-rich motif has been highly conserved during evolution. This conclusion, taken together with the observed permissiveness of a variety of eukaryotic cell types for Rev function, suggests that the target for the activation domain of Rev is likely to be a highly conserved cellular protein(s) intrinsic to nuclear mRNA transport or splicing.

Related Genes
tat
MeSH Terms
Amino Acid Sequence Animals Cell Line DNA Mutational Analysis Gene Expression Regulation, Viral Gene Products, rev/chemistry,genetics,metabolism Gene Products, tat/biosynthesis,genetics HIV-1/genetics Humans Mice Molecular Sequence Data Mutagenesis, Insertional Mutagenesis, Site-Directed Plasmids Precipitin Tests Primates Proviruses/genetics Quail RNA Splicing RNA, Messenger/biosynthesis Transfection rev Gene Products, Human Immunodeficiency Virus tat Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, rev Gene Products, tat RNA, Messenger rev Gene Products, Human Immunodeficiency Virus tat Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Malim M H
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
McCarn D F
Tiley L S
Cullen B R
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.65.8.4248-4254.1991
Published
1991-08-00
Pages
4248-54
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC248862
Subset
IM
Grants
NIAID NIH HHS · AI29821 · United States
External Links
PubMed source DOI: 10.1128/JVI.65.8.4248-4254.1991 PMC Full Text View journal details
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