title: APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons.
abstract: APOBEC3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and transposition of endogenous retroelements. One family member, APOBEC3A (hA3A), is an orphan, without any known antiviral activity. We show that hA3A is catalytically active and that it, but none of the other family members, potently inhibits replication of the parvovirus adeno-associated virus (AAV). hA3A was also a potent inhibitor of the endogenous LTR retroelements, MusD, IAP, and the non-LTR retroelement, LINE-1. Its function was dependent on the conserved amino acids of the hA3A active site, consistent with a role for cytidine deamination, although mutations in retroelement sequences were not found. These findings demonstrate the potent activity of hA3A, an APOBEC3 family member with no previously identified function. They also highlight the functional differences between APOBEC3 proteins. The APOBEC3 family members have distinct functions and may have evolved to resist various classes of genetic elements.
authors.affiliation: Infectious Disease Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Lilley
authors.forename: Qin
authors.initials: Q
authors.lastname: Yu
authors.forename: Darwin V
authors.initials: DV
authors.lastname: Lee
authors.forename: Jody
authors.initials: J
authors.lastname: Chou
authors.forename: Iñigo
authors.initials: I
authors.lastname: Narvaiza
authors.forename: Nathaniel R
authors.initials: NR
authors.lastname: Landau
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D003564:Cytidine Deaminase / Q000502:physiology*; D000229:Dependovirus / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology; D009687:Nuclear Proteins / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D018626:Retroelements / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D018626:Retroelements; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase