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 journalArticlepeer-review

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

Bibliographical note

Funding Information:
This work was supported by NIAID R37 AI064046 and NIGMS R01 GM118000. A. M. M. received partial salary support from NIAID T32 AI83196, M. C. J. from NCI T32 CA009138, and D. J. S. from NIDCR T90 DE022732.

Keywords

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

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