HIV Vpr Modulates the Host DNA Damage Response at Two Independent Steps to Damage DNA and Repress Double-Strand DNA Break Repair

Author:

Li Donna1,Lopez Andrew12,Sandoval Carina12,Nichols Doyle Randilea1,Fregoso Oliver I.12ORCID

Affiliation:

1. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA

2. Molecular Biology Institute, University of California, Los Angeles, California, USA

Abstract

The DNA damage response (DDR) is a signaling cascade that safeguards the genome from genotoxic agents, including human pathogens. However, the DDR has also been utilized by many pathogens, such as human immunodeficiency virus (HIV), to enhance infection. To properly treat HIV-positive individuals, we must understand how the virus usurps our own cellular processes. Here, we have found that an important yet poorly understood gene in HIV, Vpr, targets the DDR at two unique steps: it causes damage and activates DDR signaling, and it represses the ability of cells to repair this damage, which we hypothesize is central to the primary function of Vpr. In clarifying these important functions of Vpr, our work highlights the multiple ways human pathogens engage the DDR and further suggests that modulation of the DDR is a novel way to help in the fight against HIV.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of General Medical Sciences

Burroughs Wellcome Fund

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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