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

Terumasa Ikeda, Amy M. Molan, Matthew C. Jarvis, Michael A. Carpenter, Daniel J. Salamango, William L Brown, Reuben Harris

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article number001276
Pages (from-to)1140-1152
Number of pages13
JournalJournal of General Virology
Volume100
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • APOBEC3G
  • G to A hypermutation
  • HIV-1 restriction
  • Myeloid cell line THP-1
  • Vif

PubMed: MeSH publication types

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

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