Human Herpes Simplex Virus-1 depletes APOBEC3A from nuclei

Virology. 2019 Nov:537:104-109. doi: 10.1016/j.virol.2019.08.012. Epub 2019 Aug 13.

Abstract

APOBEC3 family of DNA-cytosine deaminases inactivate and mutate several human viruses. We constructed a human cell line that is inducible for EGFP-tagged APOBEC3A and found A3A predominantly in the nuclei. When these cells were infected with Herpes Simplex Virus-1, virus titer was unaffected by A3A expression despite nuclear virus replication. When A3A expression and virus infection were monitored, A3A was found predominantly to be nuclear in infected cells up to 3 h post-infection, but was predominantly cytoplasmic by 12 h. This effect did not require the whole virus, and could be reproduced using the UL39 gene of the virus which codes for a subunit of the viral ribonucleotide reductase. These results are similar to the reported exclusion of APOBEC3B by Epstein Barr virus ortholog of UL39, BORF2, but HSV1 UL39 gene product appears better at excluding A3A than A3B from nuclei.

Keywords: Antiviral response; Cytidine deaminase; Evasion of innate antiviral immunity; Innate immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / chemistry*
  • Chlorocebus aethiops
  • Cytidine Deaminase / analysis*
  • Cytidine Deaminase / genetics
  • Cytoplasm / chemistry*
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • HeLa Cells
  • Herpesvirus 1, Human / growth & development*
  • Humans
  • Immunologic Factors / analysis*
  • Immunologic Factors / genetics
  • Proteins / analysis*
  • Proteins / genetics
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / genetics
  • Staining and Labeling
  • Vero Cells
  • Viral Proteins / biosynthesis*
  • Viral Proteins / genetics

Substances

  • Immunologic Factors
  • Proteins
  • Recombinant Fusion Proteins
  • Viral Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • APOBEC3A protein, human
  • Cytidine Deaminase