APOBEC3B lysine residues are dispensable for DNA cytosine deamination, HIV-1 restriction, and nuclear localization

Amy M. Molan, Heather M. Hanson, Cynthia M. Chweya, Brett D. Anderson, Gabriel J. Starrett, Christopher M. Richards, Reuben S. Harris

Research output: Contribution to journalArticlepeer-review

Abstract

The APOBEC3 DNA cytosine deaminase family comprises a fundamental arm of the innate immune response and is best known for retrovirus restriction. Several APOBEC3 enzymes restrict HIV-1 and related retroviruses by deaminating viral cDNA cytosines to uracils compromising viral genomes. Human APOBEC3B (A3B) shows strong virus restriction activities in a variety of experimental systems, and is subjected to tight post-translational regulation evidenced by cell-specific HIV-1 restriction activity and active nuclear import. Here we ask whether lysines and/or lysine post-translational modifications are required for these A3B activities. A lysine-free derivative of human A3B was constructed and shown to be indistinguishable from the wild-type enzyme in DNA cytosine deamination, HIV-1 restriction, and nuclear localization activities. However, lysine loss did render the protein resistant to degradation by SIV Vif. Taken together, we conclude that lysine side chains and modifications thereof are unlikely to be central to A3B function or regulation in human cells.

Original languageEnglish (US)
Pages (from-to)74-81
Number of pages8
JournalVirology
Volume511
DOIs
StatePublished - Nov 2017

Bibliographical note

Funding Information:
We thank Nadine Shaban for modeling A3Bntd, Matthew Jarvis for assistance with statistics, and Jiayi Wang for helpful comments on the manuscript. This work was supported by NIAID R37 AI064046 and NCI R21 CA206309. A.M.M. and C.M.R. received salary support from NIAID T32-AI83196, G.J.S. from a NSF Graduate Research Fellowship 00039202, and B.D.A. from NIAID F31 AI116305. R.S.H. is the Margaret Harvey Schering Land Grant Chair for Cancer Research, a Distinguished McKnight University Professor, and an Investigator of the Howard Hughes Medical Institute. R.S.H. is a co-founder, shareholder, and consultant of ApoGen Biotechnologies Inc. The other authors declare no competing financial interests.

Keywords

  • APOBEC3B
  • DNA deamination
  • HIV-1 restriction
  • Modification
  • Posttranslational
  • Vif

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