title: Functions, structure, and read-through alternative splicing of feline APOBEC3 genes.
abstract: BACKGROUND
  Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene.
  
  
  RESULTS
  Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three very similar A3C genes (a-c), probably generated after two consecutive gene duplications. In addition to these four one-domain A3 proteins, a fifth A3, designated A3CH, is expressed by read-through alternative splicing. Specific feline A3 proteins selectively inactivated only defined genera of feline retroviruses: Bet-deficient feline foamy virus was mainly inactivated by feA3Ca, feA3Cb, and feA3Cc, while feA3H and feA3CH were only weakly active. The infectivity of Vif-deficient feline immunodeficiency virus and feline leukemia virus was reduced only by feA3H and feA3CH, but not by any of the feA3Cs. Within Felidae, A3C sequences show significant adaptive selection, but unexpectedly, the A3H sequences present more sites that are under purifying selection.
  
  
  CONCLUSIONS
  Our data support a complex evolutionary history of expansion, divergence, selection and individual extinction of antiviral A3 genes that parallels the early evolution of Placentalia, becoming more intricate in taxa in which the arms race between host and retroviruses is harsher.
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany. mueca@pei.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Münk
authors.forename: Thomas
authors.initials: T
authors.lastname: Beck
authors.forename: Jörg
authors.initials: J
authors.lastname: Zielonka
authors.forename: Agnes
authors.initials: A
authors.lastname: Hotz-Wagenblatt
authors.forename: Sarah
authors.initials: S
authors.lastname: Chareza
authors.forename: Marion
authors.initials: M
authors.lastname: Battenberg
authors.forename: Jens
authors.initials: J
authors.lastname: Thielebein
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
authors.forename: Ignacio G
authors.initials: IG
authors.lastname: Bravo
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Martin
authors.initials: M
authors.lastname: Löchelt
authors.forename: Naoya
authors.initials: N
authors.lastname: Yuhki
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats / Q000378:metabolism / Q000821:virology; D043525:Cytosine Deaminase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005784:Gene Amplification; D015870:Gene Expression; D023061:Gene Order; D014644:Genetic Variation; D016678:Genome; D008969:Molecular Sequence Data; D010802:Phylogeny; D012190:Retroviridae / Q000502:physiology; D014779:Virus Replication
chemical_list: D043525:Cytosine Deaminase