Mechanisms of late restriction induced by an endogenous retrovirus.
The host has developed during evolution a variety of "restriction factors" to fight retroviral infections. We investigated the mechanisms of a unique viral block acting at late stages of the retrovirus replication cycle. The sheep genome is colonized by several copies of endogenous retroviruses, known as enJSRVs, which are highly related to the oncogenic jaagsiekte sheep retrovirus (JSRV). enJS56A1, one of the enJSRV proviruses, can act as a restriction factor by blocking viral particles release of the exogenous JSRV. We show that in the absence of enJS56A1 expression, the JSRV Gag (the retroviral internal structural polyprotein) targets initially the pericentriolar region, in a dynein and microtubule-dependent fashion, and then colocalizes with the recycling endosomes. Indeed, by inhibiting the endocytosis and trafficking of recycling endosomes we hampered JSRV exit from the cell. Using a variety of approaches, we show that enJS56A1 and JSRV Gag interact soon after synthesis and before pericentriolar/recycling endosome targeting of the latter. The transdominant enJS56A1 induces intracellular Gag accumulation in microaggregates that colocalize with the aggresome marker GFP-250 but develop into bona fide aggresomes only when the proteasomal machinery is inhibited. The data argue that dominant-negative proteins can modify the overall structure of Gag multimers/viral particles hampering the interaction of the latter with the cellular trafficking machinery.
Arnaud
Frederick
F
Institute of Comparative Medicine, University of Glasgow Veterinary School, 464 Bearsden Road, Glasgow, G61 1QH Scotland, United Kingdom.
Murcia
Pablo R
PR
Palmarini
Massimo
M
D000818:Animals; D001692:Biological Transport; D020077:Endogenous Retroviruses / Q000472:pathogenicity*; D011992:Endosomes / Q000821:virology*; D015683:Gene Products, gag / Q000378:metabolism; D016679:Genome, Viral; D012756:Sheep; D014771:Virion
D015683:Gene Products, gag
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14390-5
16980413
Mol Biol Cell. 2007 Jun;18(6):2102-11
17392513
PLoS Biol. 2006 Dec;4(12):e435
17147474
Int Rev Cytol. 2000;192:189-221
10553280
J Virol. 2000 Sep;74(17):8065-76
10933716
J Virol. 2001 Dec;75(23):11319-27
11689612
J Natl Cancer Inst. 2001 Nov 7;93(21):1603-14
11698564
Nature. 2002 Aug 8;418(6898):646-50
12167863
J Virol. 2003 Jan;77(1):749-53
12477881
Curr Top Microbiol Immunol. 2003;275:117-37
12596897
Trends Microbiol. 2003 Jun;11(6):286-91
12823946
Curr Biol. 2003 Aug 5;13(15):R614-24
12906817
Traffic. 2003 Oct;4(10):660-70
12956869
Traffic. 2003 Oct;4(10):671-80
12956870
J Gen Virol. 2004 Jan;85(Pt 1):1-13
14718613
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10774-9
15249685
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10780-5
15249687
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10786-91
15249690
Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11117-22
15263098
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11827-32
15280539
Nat Immunol. 2004 Nov;5(11):1109-15
15496950
Jpn J Exp Med. 1975 Dec;45(6):473-8
1232464
J Virol. 1987 Apr;61(4):1045-53
3493352
J Virol. 1990 Aug;64(8):3844-52
2370682
J Virol. 1990 Sep;64(9):4383-9
2200887
Trends Biotechnol. 1994 May;12(5):193-8
7764903
J Cell Biol. 1996 Feb;132(4):617-33
8647893
Science. 1996 Mar 15;271(5255):1539-44
8599110
Nature. 1996 Aug 29;382(6594):826-9
8752279
J Cell Biol. 1996 Nov;135(4):913-24
8922376
Trends Microbiol. 1997 Aug;5(8):313-8
9263409
Eur J Cell Biol. 1998 Apr;75(4):344-52
9628320
J Cell Sci. 1999 May;112 ( Pt 9):1303-11
10194409
Mol Membr Biol. 1999 Jan-Mar;16(1):81-7
10332741
J Virol. 1999 Jul;73(7):5431-7
10364290
J Virol. 1999 Aug;73(8):6964-72
10400795
J Cell Biol. 1999 Sep 20;146(6):1239-54
10491388
J Virol. 2005 Mar;79(6):3775-86
15731271
Placenta. 2006 Apr;27 Suppl A:S135-40
16533524
Traffic. 2006 May;7(5):516-23
16643275
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7465-70
16648264
Virology. 2006 Jul 5;350(2):347-57
16500691
J Virol. 2007 Feb;81(4):1762-72
17135320
J Virol. 2007 Mar;81(5):2138-48
17135314
Nat Med. 2007 May;13(5):631-5
17435772
J Virol. 2007 Feb;81(3):1054-61
16956947