APOBEC3B is one of seven human APOBEC3 DNA cytosine deaminases that function to inhibit the replication and persistence of retroelements and retroviruses. Human APOBEC3B restricts the replication of HIV-1 in HEK293 cells, while our laboratory clone of rhesus macaque APOBEC3B did not. We mapped the restriction determinant to a single amino acid difference that alters enzymatic activity. Human APOBEC3B D316 is catalytically active and capable of restricting HIV-1 while rhesus APOBEC3B N316 is not; swapping these residues alters the activity and restriction phenotypes respectively. Genotyping of primate center rhesus macaques revealed uniform homozygosity for aspartate at position 316. Considering the C-to-T nature of the underlying mutation, we suspect that our rhesus APOBEC3B cDNA was inactivated by its own gene product during subcloning in Escherichia coli. This region has been previously characterized for its role in substrate specificity, but these data indicate it also has a fundamental role in deaminase activity.
Bibliographical noteFunding Information:
We thank Drs. Greg Wilkerson and Welkin Johnson for providing rhesus macaque samples and the NIH AIDS Research and Reference Reagent Program for materials. This research was funded by NIH R01 AI064046 and P01 GM091743 to RSH and NIH R01 GM093086 to SLS. JFH was supported in part by a UMN Graduate Student Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright 2013 Elsevier B.V., All rights reserved.
- DNA cytosine deamination
- Human immunodeficiency virus-type 1 (HIV-1)
- Restriction factors
- Rhesus macaque