The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection

Authors

Laurieann Klockow, Marquette UniversityFollow
Hamayun J. Sharifi, Albany Medical College
Xiaoyun Wen, Emory University
Meg Flagg, Albany Medical College
Andrea K.M. Furuya, Albany Medical College
Michael Nekorchuk, Albany Medical College
Carlos M.C. de Noronha, Albany Medical College

Document Type

Article

Language

eng

Publication Date

9-2013

Publisher

Elsevier

Source Publication

Virology

Source ISSN

0042-6822

Original Item ID

DOI: 10.1016/j.virol.2013.06.010

Abstract

The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4^DCAF1 ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4^DCAF1. Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4^DCAF1. We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T cells. We demonstrate that Dicer also restricts HIV-1 replication in human monocyte-derived macrophages (MDM) and that reducing Dicer expression in MDMs enhances HIV-1 infection in a Vpr-dependent manner. Our results support a model in which Vpr complexes with human Dicer to boost its interaction with the CRL4^DCAF1 ubiquitin ligase complex and its subsequent degradation.

Comments

Accepted version. Virology, Vol. 444, No. 1-2 (September 2013): 191-202. DOI. © 2013 Elsevier. Used with permission.

NOTICE: this is the author’s version of a work that was accepted for publication in Virology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Virology, VOL 444, ISSUE 1-2, September 2013, DOI.

Recommended Citation

Klockow, Laurieann; Sharifi, Hamayun J.; Wen, Xiaoyun; Flagg, Meg; Furuya, Andrea K.M.; Nekorchuk, Michael; and de Noronha, Carlos M.C., "The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection" (2013). Biomedical Sciences Faculty Research and Publications. 32.
https://epublications.marquette.edu/biomedsci_fac/32