HIV-1 Vpr degrades the HLTF DNA translocase in T cells and macrophages

Abstract

Significance Human immunodeficiency viruses (HIV) have developed strategies to interfere with DNA repair in host cells. Some DNA repair pathways represent restriction mechanisms that counteract the virus as soon as it penetrates into the host cell, before the establishment of an interferon response. Here we identify helicase-like transcription factor (HLTF) as a new protein degraded by the viral protein R (Vpr) from HIV-1. HLTF mediates the repair of stalled replication forks to bypass DNA lesions and ensure genome integrity. HLTF is degraded early after Vpr delivery to T lymphocytes or macrophages that represent relevant target cells for HIV. The discovery of HLTF as a DNA repair protein degraded by Vpr in infected cells paves the way for novel unexpected restriction mechanisms.