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PMID: 9436978 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection.

Genes & development ·Vol. 12 ·No. 2 ·1998-01-15 ·Pages 175-85

Vodicka MA, Koepp DM, Silver PA, Emerman M

Abstract

HIV-1 Vpr promotes nuclear entry of viral nucleic acids in nondividing macrophages and also causes a G2 cell-cycle arrest. Consistent with its role in nuclear transport, we show Vpr localizes to the nuclear envelope in both human and yeast cells. Like the importin-beta subunit of the nuclear import receptor, Vpr also interacts with the yeast importin-alpha subunit and nucleoporins. Moreover, overexpression of either Vpr or importin-beta in yeast blocks nuclear transport of mRNAs. A mutant form of Vpr (Vpr F34I) that does not localize at the nuclear envelope, or bind to importin-alpha and nucleoporins, renders HIV-1 incapable of infecting macrophages efficiently. Vpr F34I, however, still causes a G2 arrest, demonstrating that the dual functions of Vpr are genetically separable. Our data suggest Vpr functionally resembles importin-beta in nuclear import of the HIV-1 pre-integration complex and this function is essential for the role of Vpr in macrophage infection, but not G2 arrest.

MeSH Terms
Cell Nucleus/metabolism,virology Cells, Cultured Fluorescent Antibody Technique, Indirect G2 Phase/genetics Gene Products, vpr/genetics,metabolism,physiology HIV-1/genetics,pathogenicity HeLa Cells Humans Macrophages/virology Nuclear Envelope/metabolism Nuclear Proteins/metabolism Point Mutation RNA, Messenger/analysis T-Lymphocytes/virology Yeasts/metabolism alpha Karyopherins beta Karyopherins vpr Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, vpr Nuclear Proteins RNA, Messenger alpha Karyopherins beta Karyopherins vpr Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vodicka M A
Divisions of Molecular Medicine and Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 USA.
Koepp D M
Silver P A
Emerman M
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.2.175
Published
1998-01-15
Pages
175-85
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316441
Subset
IM
Grants
PHS HHS · R01A130927 · United States
NIGMS NIH HHS · R01GM36373 · United States
NHLBI NIH HHS · P01HL53762 · United States
External Links
PubMed source DOI: 10.1101/gad.12.2.175 PMC Full Text View journal details
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