title: The breadth of antiviral activity of Apobec3DE in chimpanzees has been driven by positive selection.
abstract: The Apobec3 family of cytidine deaminases can inhibit the replication of retroviruses and retrotransposons. Human and chimpanzee genomes encode seven Apobec3 paralogs; of these, Apobec3DE has the greatest sequence divergence between humans and chimpanzees. Here we show that even though human and chimpanzee Apobec3DEs are very divergent, the two orthologs similarly restrict long terminal repeat (LTR) and non-LTR retrotransposons (MusD and Alu, respectively). However, chimpanzee Apobec3DE also potently restricts two lentiviruses, human immunodeficiency virus type 1 (HIV-1) and the simian immunodeficiency virus (SIV) that infects African green monkeys (SIVagmTAN), unlike human Apobec3DE, which has poor antiviral activity against these same viruses. This difference between human and chimpanzee Apobec3DE in the ability to restrict retroviruses is not due to different levels of Apobec3DE protein incorporation into virions but rather to the ability of Apobec3DE to deaminate the viral genome in target cells. We further show that Apobec3DE rapidly evolved in chimpanzee ancestors approximately 2 to 6 million years ago and that this evolution drove the increased breadth of chimpanzee Apobec3DE antiviral activity to its current high activity against some lentiviruses. Despite a difference in target specificities between human and chimpanzee Apobec3DE, Apobec3DE is likely to currently play a role in host defense against retroelements in both species.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA.
authors.forename: Nisha K
authors.initials: NK
authors.lastname: Duggal
authors.forename: Harmit S
authors.initials: HS
authors.lastname: Malik
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000818:Animals; D002460:Cell Line; D016000:Cluster Analysis; D043525:Cytosine Deaminase / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010802:Phylogeny; D011995:Recombination, Genetic; D018626:Retroelements / Q000276:immunology*; D012190:Retroviridae / Q000276:immunology*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014779:Virus Replication
chemical_list: D018626:Retroelements; D043525:Cytosine Deaminase