title: Mouse APOBEC3 restricts friend leukemia virus infection and pathogenesis in vivo.
abstract: Several members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like complex 3 (APOBEC3) family in primates act as potent inhibitors of retroviral replication. However, lentiviruses have evolved mechanisms to specifically evade host APOBEC3. Likewise, murine leukemia viruses (MuLV) exclude mouse APOBEC3 from the virions and cleave virion-incorporated APOBEC3. Although the betaretrovirus mouse mammary tumor virus has been shown to be susceptible to mouse APOBEC3, it is not known if APOBEC3 has a physiological role in restricting more widely distributed and long-coevolved mouse gammaretroviruses. The pathogenicity of Friend MuLV (F-MuLV) is influenced by several host genes: some directly restrict the cell entry or integration of the virus, while others influence the host immune responses. Among the latter, the Rfv3 gene has been mapped to chromosome 15 in the vicinity of the APOBEC3 locus. Here we have shown that polymorphisms at the mouse APOBEC3 locus indeed influence F-MuLV replication and pathogenesis: the APOBEC3 alleles of F-MuLV-resistant C57BL/6 and -susceptible BALB/c mice differ in their sequences and expression levels in the hematopoietic tissues and in their abilities to restrict F-MuLV replication both in vitro and in vivo. Furthermore, upon infection with the pathogenic Friend virus complex, (BALB/c x C57BL/6)F(1) mice displayed an exacerbated erythroid cell proliferation when the mice carried a targeted disruption of the C57BL/6-derived APOBEC3 allele. These results indicate, for the first time, that mouse APOBEC3 is a physiologically functioning restriction factor to mouse gammaretroviruses.
authors.affiliation: Department of Immunology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. masaaki@med.kindai.ac.jp
authors.forename: Eri
authors.initials: E
authors.lastname: Takeda
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Tsuji-Kawahara
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Langlois
authors.forename: Michael S
authors.initials: MS
authors.lastname: Neuberger
authors.forename: Cristina
authors.initials: C
authors.lastname: Rada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D007942:Leukemia, Experimental / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D012192:Retroviridae Infections / Q000276:immunology; D016415:Sequence Alignment; D014412:Tumor Virus Infections / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase
references.citation: PLoS One. 2007 Sep 12;2(9):e893
references.pmid: 17849022
references.citation: Mol Cell. 2003 Sep;12(3):591-601
references.pmid: 14527406
references.citation: J Infect Dis. 2007 Apr 1;195(7):960-4
references.pmid: 17330785
references.citation: J Biol Chem. 2003 Nov 7;278(45):44412-6
references.pmid: 12970355
references.citation: J Virol. 2005 Jul;79(13):8201-7
references.pmid: 15956565
references.citation: PLoS Biol. 2004 Sep;2(9):E275
references.pmid: 15269786
references.citation: Curr Biol. 2005 Jan 26;15(2):166-70
references.pmid: 15668174
references.citation: Nat Med. 2003 Nov;9(11):1398-403
references.pmid: 14528301
references.citation: J Virol. 2001 Apr;75(7):3152-63
references.pmid: 11238842
references.citation: Br J Haematol. 2000 May;109(2):280-7
references.pmid: 10848813
references.citation: J Virol. 2005 Sep;79(17):11513-6
references.pmid: 16103203
references.citation: Cell. 2003 Jun 13;113(6):803-9
references.pmid: 12809610
references.citation: Curr Biol. 2003 Nov 11;13(22):2009-13
references.pmid: 14614829
references.citation: AIDS Rev. 2004 Jan-Mar;6(1):34-9
references.pmid: 15168739
references.citation: J Mol Biol. 2004 Mar 26;337(3):585-96
references.pmid: 15019779
references.citation: Curr Biol. 2006 Aug 8;16(15):1565-70
references.pmid: 16890533
references.citation: J Virol. 2004 Jun;78(12):6322-34
references.pmid: 15163726
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12260-5
references.pmid: 15297622
references.citation: Int Immunol. 2006 Jan;18(1):183-98
references.pmid: 16352628
references.citation: Vaccine. 2008 Jun 6;26(24):2981-96
references.pmid: 18255203
references.citation: J Virol. 1999 Sep;73(9):7848-52
references.pmid: 10438878
references.citation: Annu Rev Immunol. 1990;8:477-99
references.pmid: 2188671
references.citation: Proc Natl Acad Sci U S A. 1979 Jan;76(1):425-9
references.pmid: 284359
references.citation: J Virol. 1995 Apr;69(4):2617-20
references.pmid: 7884913
references.citation: J Virol. 2008 Feb;82(3):1305-13
references.pmid: 18032489
references.citation: J Virol Methods. 1991 Oct;34(3):255-71
references.pmid: 1744218
references.citation: J Immunol. 1992 Jan 15;148(2):644-7
references.pmid: 1729380
references.citation: J Biol Chem. 2006 Dec 1;281(48):36624-31
references.pmid: 17020885
references.citation: J Virol. 2006 Jan;80(2):605-14
references.pmid: 16378963
references.citation: Virology. 1981 Jul 15;112(1):131-44
references.pmid: 6787798
references.citation: AIDS. 2005 Jul 1;19(10):1015-24
references.pmid: 15958832
references.citation: Curr Biol. 2004 Aug 10;14(15):1385-91
references.pmid: 15296757
references.citation: J Immunol. 1992 Mar 15;148(6):1964-7
references.pmid: 1541833
references.citation: Curr Top Microbiol Immunol. 1989;148:1-42
references.pmid: 2684547
references.citation: PLoS Genet. 2007 Oct;3(10):2014-22
references.pmid: 17967065
references.citation: Science. 2003 Nov 7;302(5647):1056-60
references.pmid: 14564014
references.citation: Virology. 2005 Mar 15;333(2):374-86
references.pmid: 15721369
references.citation: Cell. 2003 Jul 11;114(1):21-31
references.pmid: 12859895
references.citation: J Exp Med. 1988 Nov 1;168(5):1587-605
references.pmid: 3141552
references.citation: Nature. 2005 May 5;435(7038):108-14
references.pmid: 15829920
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15588-93
references.pmid: 17030807
references.citation: Cell. 1986 Dec 26;47(6):851-9
references.pmid: 3465451
references.citation: Trends Immunol. 2006 Jun;27(6):291-7
references.pmid: 16678488
references.citation: Nature. 2003 Jul 3;424(6944):99-103
references.pmid: 12808466
references.citation: Nature. 2007 Feb 22;445(7130):927-30
references.pmid: 17259974
references.citation: Mol Cell Biol. 2005 Aug;25(16):7270-7
references.pmid: 16055735
references.citation: J Virol. 1999 May;73(5):4327-40
references.pmid: 10196331
references.citation: Nature. 2005 Jan 27;433(7024):430-3
references.pmid: 15674295