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PMID: 8642662 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: identification of a family of transferable nuclear export signals.

Journal of virology ·Vol. 70 ·No. 4 ·1996-04-00 ·Pages 2350-9

Meyer BE, Meinkoth JL, Malim MH

Abstract

The human immunodeficiency virus type 1 Rev trans activator binds directly to unspliced viral mRNA in the nucleus and activates its transport to the cytoplasm. In additon to the sequences that confer RNA binding and nuclear localization, Rev has a carboxy-terminal region, the activation domain, whose integrity is essential for biological activity. Because it has been established that Rev constitutively exits and reenters the nucleus and that the activation domain is required for nuclear exit, it has been proposed that Rev's activation domain is a nuclear export signal (NES). Here, we used microinjection-based assays to demonstrate that the activation domain of human immunodeficiency virus type 1 Rev imparts rapid nuclear export after its transfer to heterologous substrates. NES- mediated export is specific, as it is sensitive both to inactivation by missense mutation and to selective inhibition by an excess of the wild-type, but not mutant, activation domain peptide. Examination of the Rev trans activators of two nonprimate lentiviruses, visna virus and equine infectious anemia virus, revealed that their activation domains are also potent NESs. Taken together, these data demonstrate that nuclear export can be determined by positively acting peptide motifs, namely, NESs, and suggest that Rev proteins activate viral RNA transport by providing export ribonucleoproteins with specific information that targets them to the cytoplasm.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Biological Transport Cell Nucleus/metabolism,virology Gene Products, rev/genetics,metabolism HIV-1/metabolism HeLa Cells Humans Infectious Anemia Virus, Equine/metabolism Molecular Sequence Data Protein Sorting Signals/metabolism Temperature Visna-maedi virus/metabolism rev Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, rev Protein Sorting Signals rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Meyer B E
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Meinkoth J L
Malim M H
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.70.4.2350-2359.1996
Published
1996-04-00
Pages
2350-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC190077
Subset
IM
Grants
NCI NIH HHS · CA16520 · United States
NIDDK NIH HHS · DK19525 · United States
NIDDK NIH HHS · DK45696 · United States
External Links
PubMed source DOI: 10.1128/JVI.70.4.2350-2359.1996 PMC Full Text View journal details
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