title: The signal peptide of a recently integrated endogenous sheep betaretrovirus envelope plays a major role in eluding gag-mediated late restriction.
abstract: The exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV) coexists with highly related and biologically active endogenous retroviruses (enJSRVs). The endogenous enJS56A1 locus possesses a defective Gag polyprotein which blocks the late replication steps of related exogenous and endogenous retroviruses by a mechanism known as JSRV late restriction (JLR). Conversely, enJSRV-26, which most likely integrated into the sheep genome less than 200 years ago, is able to escape JLR. In this study, we demonstrate that the ability of enJSRV-26 to escape JLR is due to a single-amino-acid substitution in the signal peptide (SP) of its envelope glycoprotein. We show that enJSRV-26 SP does not localize to the nucleolus, unlike the functional SPs of related exogenous and endogenous sheep betaretroviruses. In addition, enJSRV-26 SP function as a posttranscriptional regulator of viral gene expression is impaired. enJSRV-26 JLR escape relies on the presence of the functional enJS56A1 SP. Moreover, we show that the ratio between enJSRV-26 and enJS56A1 Gag is critical to elude JLR. Interestingly, we found that the domestic sheep has acquired, by genome amplification, several copies of the enJS56A1 provirus. These data further reinforce the notion that transdominant enJSRV proviruses have been positively selected in domestic sheep, and that the coevolution between endogenous and exogenous sheep betaretroviruses and their host is still occurring.
authors: MRC, University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Q61 1QH, United Kingdom.
authors: Alessia
authors: A
authors: Armezzani
authors: Frédérick
authors: F
authors: Arnaud
authors: Marco
authors: M
authors: Caporale
authors: Giuliapia
authors: G
authors: di Meo
authors: Leopoldo
authors: L
authors: Iannuzzi
authors: Claudio
authors: C
authors: Murgia
authors: Massimo
authors: M
authors: Palmarini
references: J Gen Virol. 2004 Jan;85(Pt 1):1-13
references: 14718613
references: Nucleic Acids Res. 1990 Apr 25;18(8):2037-44
references: 2186373
references: J Virol. 2007 Feb;81(4):1762-72
references: 17135320
references: J Virol. 2010 May;84(9):4415-25
references: 20181686
references: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12127-32
references: 19564597
references: J Virol. 2005 Dec;79(23):14737-47
references: 16282474
references: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14390-5
references: 16980413
references: Placenta. 2006 Apr;27 Suppl A:S135-40
references: 16533524
references: Curr Opin Cell Biol. 1990 Aug;2(4):604-8
references: 2252586
references: Retrovirology. 2009 Feb 03;6:10
references: 19192308
references: Reprod Fertil Dev. 2007;19(1):65-78
references: 17389136
references: Ann N Y Acad Sci. 2009 Oct;1178:157-72
references: 19845636
references: Annu Rev Genet. 2008;42:709-32
references: 18694346
references: J Virol. 2009 Dec;83(23):12483-98
references: 19776124
references: J Virol. 2003 Jan;77(1):749-53
references: 12477881
references: J Virol. 1999 Dec;73(12):10070-8
references: 10559321
references: PLoS Pathog. 2007 Nov;3(11):e170
references: 17997604
references: J Virol. 2000 Sep;74(17):8065-76
references: 10933716
references: J Virol. 1992 Apr;66(4):2510-3
references: 1548775
references: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):725-30
references: 15644441
references: Cell Mol Life Sci. 2008 Nov;65(21):3422-32
references: 18818869
references: Retrovirology. 2008 Jan 28;5:8
references: 18226242
references: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60
references: 8108397
references: EMBO J. 1997 Nov 17;16(22):6636-45
references: 9362478
references: J Virol. 2006 Mar;80(6):3104-7
references: 16501122
references: Cytogenet Cell Genet. 2001;92(3-4):283-99
references: 11435702
references: J Biol Chem. 2009 Sep 18;284(38):25642-52
references: 19632991
references: J Virol. 2009 May;83(9):4591-604
references: 19244321
references: Cell. 1995 Aug 25;82(4):531-3
references: 7664331
references: J Virol. 1990 Aug;64(8):3844-52
references: 2370682
references: Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12287-92
references: 20566871
references: Nature. 2006 Jul 6;442(7098):79-81
references: 16823453
references: Annu Rev Cell Biol. 1994;10:87-119
references: 7888184
references: Traffic. 2003 Oct;4(10):671-80
references: 12956870
references: Science. 2009 Apr 24;324(5926):532-6
references: 19390051
references: J Virol. 2007 Oct;81(20):11441-51
references: 17699582
references: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11117-22
references: 15263098
references: Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9
references: 2784208
references: J Virol. 1999 Aug;73(8):6964-72
references: 10400795
references: Virology. 2006 Jul 5;350(2):347-57
references: 16500691
references: J Virol. 2000 Apr;74(7):3321-9
references: 10708449
references: Cell Mol Life Sci. 2008 Nov;65(21):3325-8
references: 18818876