UMMS Affiliation

Program in Molecular Medicine

Publication Date

2008-05-03

Document Type

Article

Subjects

Animals; COS Cells; Cercopithecus aethiops; DNA-Binding Proteins; Gene Expression Regulation, Viral; Gene Silencing; HIV-2; Leukocytes, Mononuclear; Macrophages; RNA Interference; RNA, Small Interfering; Recombinant Fusion Proteins; Viral Regulatory and Accessory Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Primate lentiviruses encode four "accessory proteins" including Vif, Vpu, Nef, and Vpr/Vpx. Vif and Vpu counteract the antiviral effects of cellular restrictions to early and late steps in the viral replication cycle. We present evidence that the Vpx proteins of HIV-2/SIV(SM) promote virus infection by antagonizing an antiviral restriction in macrophages. Fusion of macrophages in which Vpx was essential for virus infection, with COS cells in which Vpx was dispensable for virus infection, generated heterokaryons that supported infection by wild-type SIV but not Vpx-deleted SIV. The restriction potently antagonized infection of macrophages by HIV-1, and expression of Vpx in macrophages in trans overcame the restriction to HIV-1 and SIV infection. Vpx was ubiquitylated and both ubiquitylation and the proteasome regulated the activity of Vpx. The ability of Vpx to counteract the restriction to HIV-1 and SIV infection was dependent upon the HIV-1 Vpr interacting protein, damaged DNA binding protein 1 (DDB1), and DDB1 partially substituted for Vpx when fused to Vpr. Our results indicate that macrophage harbor a potent antiviral restriction and that primate lentiviruses have evolved Vpx to counteract this restriction.

Rights and Permissions

Copyright: © 2008 Sharova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version

10.1371/journal.ppat.1000057

Source

PLoS Pathog. 2008 May 2;4(5):e1000057. Link to article on publisher's site

Journal/Book/Conference Title

PLoS pathogens

Related Resources

Link to Article in PubMed

PubMed ID

18451984

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