Functions, structure, and read-through alternative splicing of feline APOBEC3 genes

Carsten Münk¹ , Thomas Beck² , Jörg Zielonka¹ , Agnes Hotz-Wagenblatt³ , Sarah Chareza⁴ , Marion Battenberg¹ , Jens Thielebein⁵ , Klaus Cichutek¹ , Ignacio G Bravo⁶ , Stephen J O'Brien⁷ , Martin Lochelt⁴ and Naoya Yuhki⁷

¹Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany

²SAIC-Frederick, Inc., NCI-Frederick, Laboratory of Genomic Diversity, Frederick, MD 21702-1201, USA

³Department of Molecular Biophysics, Research Program Structural and Functional Genomics, German Cancer Research Center, 69120 Heidelberg, Germany

⁴Department of Genome Modifications and Carcinogenesis, Research Program Infection and Cancer, German Cancer Research Center, Heidelberg, Germany

⁵Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, 06108 Halle, Germany

⁶Institute for Evolution and Biodiversity, Westfälische Wilhems University Münster, 48143 Münster, Germany

⁷Laboratory of Genomic Diversity, NCI at Frederick, Frederick, MD 21702-1201, USA

author email corresponding author email

Genome Biology 2008, 9:R48doi:10.1186/gb-2008-9-3-r48


Published:	3 March 2008

Subject areas: Evolution, Molecular biology, Virology

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.

Conclusion

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.