Cell Cycle Regulation in Macrophages and Susceptibility to HIV-1

Viruses. 2020 Jul 31;12(8):839. doi: 10.3390/v12080839.

Abstract

Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable plasticity in their phenotypes and function provides them with the ability to quickly respond to environmental changes and infection. Recent work shows that macrophages undergo cell cycle transition from a G0/terminally differentiated state to a G1 state. This G0-to-G1 transition presents a window of opportunity for HIV-1 infection. Macrophages are an important target for HIV-1 but express high levels of the deoxynucleotide-triphosphate hydrolase SAMHD1, which restricts viral DNA synthesis by decreasing levels of dNTPs. While the G0 state is non-permissive to HIV-1 infection, a G1 state is very permissive to HIV-1 infection. This is because macrophages in a G1 state switch off the antiviral restriction factor SAMHD1 by phosphorylation, thereby allowing productive HIV-1 infection. Here, we explore the macrophage cell cycle and the interplay between its regulation and permissivity to HIV-1 infection.

Keywords: G0/G1 phase; HIV; SAMHD1; cell arrest; cell cycle; macrophage.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle Checkpoints
  • Cell Cycle*
  • Cells, Cultured
  • DNA Damage
  • G1 Phase
  • Gram-Negative Bacteria / immunology
  • HIV-1 / physiology*
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Macrophages / immunology
  • Macrophages / physiology*
  • Macrophages / virology*
  • Phosphorylation
  • Resting Phase, Cell Cycle
  • SAM Domain and HD Domain-Containing Protein 1 / metabolism
  • vif Gene Products, Human Immunodeficiency Virus / metabolism
  • vpr Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Histone Deacetylase Inhibitors
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • vpr Gene Products, Human Immunodeficiency Virus
  • vpr protein, Human immunodeficiency virus 1
  • SAM Domain and HD Domain-Containing Protein 1