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PMID: 8947037 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIV(SM).

The EMBO journal ·Vol. 15 ·No. 22 ·1996-11-15 ·Pages 6155-65

Fletcher TM, Brichacek B, Sharova N, Newman MA, Stivahtis G, Sharp PM, Emerman M, Hahn BH, Stevenson M

Abstract

The vpr genes of human and simian immunodeficiency viruses (HIV/SIV) encode proteins which are packaged in the virus particle. HIV-1 Vpr has been shown to mediate the nuclear import of viral reverse transcription complexes in non-dividing target cells (e.g. terminally differentiated macrophages), and to alter the cell cycle and proliferation status of the infected host cell. Members of the HIV-2/SIV(SM) group encode, in addition to Vpr, a related protein called Vpx. Because these two proteins share considerable sequence similarity, it has been assumed that they also exhibit similar functions. Here, we report that the functions of Vpr and Vpx are distinct and non-redundant, although both proteins are components of the HIV-2/SIV(SM) virion and reverse transcription complex. Characterizing SIV(SM) proviruses defective in one or both genes, we found that Vpx is both necessary and sufficient for the nuclear import of the viral reverse transcription complex. In contrast, Vpr, but not Vpx, inhibited the progression of infected host cells from the G2 to the M phase of the cell cycle. Thus, two independent functions of the HIV-1 Vpr protein are encoded by separate genes in HIV-2/SIV(SM). This segregation is consistent with the conservation of these genes in HIV-2/SIV(SM) evolution, and underscores the importance of both nuclear transport and cell cycle arrest functions in primate lentivirus biology.

MeSH Terms
Animals Blotting, Western Cell Cycle/genetics Cell Division/drug effects Cell Nucleus/metabolism Cells, Cultured DNA, Viral/metabolism Gene Products, gag/metabolism Gene Products, vpr/metabolism,pharmacology Genes, Viral/genetics HIV-2/genetics,metabolism Haplorhini Macrophages/metabolism,virology Mutagenesis, Site-Directed/genetics RNA-Directed DNA Polymerase/metabolism Viral Regulatory and Accessory Proteins/metabolism,pharmacology vpr Gene Products, Human Immunodeficiency Virus
Chemicals
DNA, Viral Gene Products, gag Gene Products, vpr VPX protein, Human immunodeficiency virus 2 Viral Regulatory and Accessory Proteins vpr Gene Products, Human Immunodeficiency Virus RNA-Directed DNA Polymerase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Fletcher T M
Department of Medicine, University of Alabama, Birmingham 35294, USA.
Brichacek B
Sharova N
Newman M A
Stivahtis G
Sharp P M
Emerman M
Hahn B H
Stevenson M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-11-15
Pages
6155-65
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452436
Subset
IM
Grants
NIAID NIH HHS · AI37475 · United States
NIAID NIH HHS · N01 AI34748 · United States
NCRR NIH HHS · RR11589 · United States
External Links
PubMed source PMC Full Text View journal details
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