HIV-1 restriction by endogenous APOBEC3G in the myeloid cell line THP-1

J Gen Virol. 2019 Jul;100(7):1140-1152. doi: 10.1099/jgv.0.001276. Epub 2019 May 30.

Abstract

HIV-1 replication in CD4-positive T lymphocytes requires counteraction of multiple different innate antiviral mechanisms. Macrophage cells are also thought to provide a reservoir for HIV-1 replication but less is known in this cell type about virus restriction and counteraction mechanisms. Many studies have combined to demonstrate roles for APOBEC3D, APOBEC3F, APOBEC3G and APOBEC3H in HIV-1 restriction and mutation in CD4-positive T lymphocytes, whereas the APOBEC enzymes involved in HIV-1 restriction in macrophages have yet to be delineated fully. We show that multiple APOBEC3 genes including APOBEC3G are expressed in myeloid cell lines such as THP-1. Vif-deficient HIV-1 produced from THP-1 is less infectious than Vif-proficient virus, and proviral DNA resulting from such Vif-deficient infections shows strong G to A mutation biases in the dinucleotide motif preferred by APOBEC3G. Moreover, Vif mutant viruses with selective sensitivity to APOBEC3G show Vif null-like infectivity levels and similarly strong APOBEC3G-biased mutation spectra. Importantly, APOBEC3G-null THP-1 cells yield Vif-deficient particles with significantly improved infectivities and proviral DNA with background levels of G to A hypermutation. These studies combine to indicate that APOBEC3G is the main HIV-1 restricting APOBEC3 family member in THP-1 cells.

Keywords: APOBEC3G; G to A hypermutation; HIV-1 restriction; Vif; myeloid cell line THP-1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • APOBEC-3G Deaminase / genetics
  • APOBEC-3G Deaminase / metabolism*
  • HIV Infections / enzymology*
  • HIV Infections / genetics
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Mutation
  • Myeloid Cells
  • THP-1 Cells
  • Virus Replication
  • vif Gene Products, Human Immunodeficiency Virus / genetics
  • vif Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • vif Gene Products, Human Immunodeficiency Virus
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human