Incorporation of Vpr into Human Immunodeficiency Virus Type 1 Requires a Direct Interaction with the p6 Domain of the p55 Gag Precursor

Bachand, François; Yao, Xiaojian; Hrimech, Mohammed; Rougeau, Nicole; Cohen, Éric A.

doi:10.1074/jbc.274.13.9083

Cited by 99 publications

(82 citation statements)

References 51 publications

(30 reference statements)

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“…The biological activity of such forms of Vpr could not be analyzed in solution. Far-Western blotting demonstrated the binding of SDS-denatured Vpr to the viral nucleocapsid p7 NC (43), a finding not recapitulated with virus-derived Vpr (34). The optimized SPPS protocol we have now described permits the synthesis of soluble Vpr in sufficient quantities to allow structural and biological analyses.…”

Section: Discussionmentioning

confidence: 99%

“…First, according to the detection of monomeric sVpr by Western blot, the highest amount of viral Vpr analyzed corresponded to ϳ125 ng of sVpr per lane; at this concentration multimers of sVpr were not detected. Second, physical interactions between the C-terminal p6 gag domain of the Pr55 Gag polyprotein (33,34) direct the incorporation of Vpr into budding virus particles (35). Hence, the presence of at least one of the known Vpr binding partners, p6 gag , in the virus preparation may prevent homo-oligomerization of viral Vpr that was otherwise evident for isolated sVpr.…”

Section: Analysis Of Svpr By Protein Sequencing Ms and Westernmentioning

confidence: 99%

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Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest

Henklein

Bruns

Sherman

et al. 2000

Journal of Biological Chemistry

107

134

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Human immunodeficiency virus (HIV)Vpr contributes to nuclear import of the viral pre-integration complex and induces G 2 cell cycle arrest. We describe the production of synthetic Vpr that permitted the first studies on the structure and folding of the full-length protein. Vpr is unstructured at neutral pH, whereas under acidic conditions or upon addition of trifluorethanol it adopts ␣-helical structures. Vpr forms dimers in aqueous trifluorethanol, whereas oligomers exist in pure water.1 H NMR spectroscopy allows the signal assignment of N-and C-terminal amino acid residues; however, the central section of the molecule is obscured by self-association. These findings suggest that the in vivo folding of Vpr may require structure-stabilizing interacting factors such as previously described interacting cellular and viral proteins or nucleic acids. In biological studies we found that Vpr is efficiently taken up from the extracellular medium by cells in a process that occurs independent of other HIV-1 proteins and appears to be independent of cellular receptors. Following cellular uptake, Vpr is efficiently imported into the nucleus of transduced cells. Extracellular addition of Vpr induces G 2 cell cycle arrest in dividing cells. Together, these findings raise the possibility that circulating forms of Vpr observed in HIV-infected patients may exert biological effects on a broad range of host target cells.

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Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Svpr By Protein Sequencing Ms and Westernmentioning

confidence: 99%

Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest

Henklein

Bruns

Sherman

et al. 2000

Journal of Biological Chemistry

107

134

View full text Add to dashboard Cite

show abstract

“…Vpr is incorporated into HIV-1 virions through direct interaction with the p6 domain of the Gag protein (Bachand et al, 1999;Lavallee et al, 1994). Vpr has a variety of roles in determining HIV-1 infectivity and the number of its newly identified roles is still increasing.…”

Section: Introductionmentioning

confidence: 99%

Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

Romani

Engelbrecht

2009

Journal of General Virology

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Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is an accessory protein that interacts with a number of cellular and viral proteins. The functions of many of these interactions in the pathogenesis of HIV-1 have been identified. Deletion of the vpr gene reduces the virulence of HIV-1 dramatically, indicating the importance of this protein for the virus. This review describes the current findings on several established functions of HIV-1 Vpr and some possible roles proposed for this protein. Because Vpr exploits cellular proteins and pathways to influence the biology of HIV-1, understanding the functions of Vpr usually involves the study of cellular pathways. Several functions of Vpr are attributed to the virion-incorporated protein, but some of them are attributed to the expression of Vpr in HIV-1-infected cells. The structure of Vpr may be key to understanding the variety of its interactions. Due to the critical role of Vpr in HIV-1 pathogenicity, study of the interactions between Vpr and cellular proteins may help us to understand the mechanism(s) of HIV-1 pathogenicity.

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“…The incorporation of Vpr into particles requires a direct interaction with the p6 region of the Gag polyprotein precursor (5,6). Several independent biological activities have been attributed to Vpr during the HIV-1 life cycle.…”

mentioning

confidence: 99%

Vpr-mediated Incorporation of UNG2 into HIV-1 Particles Is Required to Modulate the Virus Mutation Rate and for Replication in Macrophages

Chen

Rouzic

Kearney

et al. 2004

Journal of Biological Chemistry

111

129

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Human immunodeficiency virus type 1 is able to infect nondividing cells, such as macrophages, and the viral Vpr protein has been shown to participate in this process. Here, we investigated the impact of the recruitment into virus particles of the nuclear form of uracil DNA glycosylase (UNG2), a cellular DNA repair enzyme, on the virus mutation rate and on replication in macrophages. We demonstrate that the interaction of Vpr with UNG2 led to virion incorporation of a catalytically active enzyme that is directly involved with Vpr in modulating the virus mutation rate. The lack of UNG in virions during virus replication in primary monocyte-derived macrophages further exacerbated virus mutant frequencies to an 18-fold increase compared with the 4-fold increase measured in actively dividing cells. Because the presence of UNG is also critical for efficient infection of macrophages, these observations extend the role of Vpr to another early step of the virus life cycle, e.g. viral DNA synthesis, that is essential for replication of human immunodeficiency virus type 1 in nondividing cells.

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Incorporation of Vpr into Human Immunodeficiency Virus Type 1 Requires a Direct Interaction with the p6 Domain of the p55 Gag Precursor

Cited by 99 publications

References 51 publications

Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest

Functional and Structural Characterization of Synthetic HIV-1 Vpr That Transduces Cells, Localizes to the Nucleus, and Induces G2 Cell Cycle Arrest

Human immunodeficiency virus type 1 Vpr: functions and molecular interactions

Vpr-mediated Incorporation of UNG2 into HIV-1 Particles Is Required to Modulate the Virus Mutation Rate and for Replication in Macrophages

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