Abstract
Viruses have been long known to perturb cell cycle regulators and key players of the DNA damage response to benefit their life cycles. In the case of the human immunodeficiency virus (HIV), the viral auxiliary protein Vpr activates the structure-specific endonuclease SLX4 complex to promote escape from innate immune sensing and, as a side effect, induces replication stress in cycling cells and subsequent cell cycle arrest at the G2/M transition. This novel pathway subverted by HIV to prevent accumulation of viral reverse transcription by-products adds up to facilitating effects of major cellular exonucleases that degrade pathological DNA species. Within this review we discuss the impact of this finding on our understanding of the interplay between HIV replication and nucleic acid metabolism and its implications for cancer-related chronic inflammation.
Highlights
Efficient human immunodeficiency virus (HIV) replication in target cells relies on its ability to use cellular resources and to overthrow host defense mechanisms
These nucleic acid sensors belong to the pattern recognition receptors (PRRs) family that recognize pathogen associated molecular patterns (PAMPs) and subsequently trigger a signaling cascade that culminates in the production of pro-inflammatory cytokines, including antiviral interferon (IFN; for review Kawai and Akira, 2006)
We recently identified the SLX4 complex as being the viral protein regulatory (Vpr) partner required for G2/M arrest (Laguette et al, 2014)
Summary
Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France. In the case of the human immunodeficiency virus (HIV), the viral auxiliary protein Vpr activates the structure-specific endonuclease SLX4 complex to promote escape from innate immune sensing and, as a side effect, induces replication stress in cycling cells and subsequent cell cycle arrest at the G2/M transition. This novel pathway subverted by HIV to prevent accumulation of viral reverse transcription by-products adds up to facilitating effects of major cellular exonucleases that degrade pathological DNA species.
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