Antiviral activity of innate immune protein ISG15.
The host innate immune response, including the production of type-I IFN, represents the primary line of defense against invading viral pathogens. Of the hundreds of IFN-stimulated genes (ISGs) discovered to date, ISG15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part, as a modifier of protein function. Evidence implicating ISG15 as an innate immune protein with broad-spectrum antiviral activity continues to accumulate rapidly. This review will summarize recent findings on the innate antiviral activity of ISG15, with a focus on the interplay between ubiquitination and ISGylation pathways resulting in modulation of RNA virus assembly/budding. Indeed, ubiquitination is known to be proviral for some RNA viruses, whereas the parallel ISGylation pathway is known to be antiviral. A better understanding of the antiviral activities of ISG15 will enhance our fundamental knowledge of host innate responses to viral pathogens and may provide insight useful for the development of novel therapeutic approaches designed to enhance the immune response against such pathogens.
Harty
Ronald N
RN
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. rharty@vet.upenn.edu
Pitha
Paula M
PM
Okumura
Atsushi
A
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004267:DNA Viruses / Q000187:drug effects*; D007113:Immunity, Innate; D051379:Mice; D012328:RNA Viruses / Q000187:drug effects*; D014452:Ubiquitins / Q000378:metabolism / Q000494:pharmacology*; D014777:Virus Diseases / Q000276:immunology / Q000821:virology
D000998:Antiviral Agents; D016207:Cytokines; D014452:Ubiquitins; C074034:ISG15 protein, human
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11199-204
11562473
PLoS One. 2007 Jul 25;2(7):e679
17653289
Autoimmunity. 2003 Dec;36(8):457-61
14984022
BMC Biochem. 2008 Oct 21;9 Suppl 1:S3
19007433
J Virol. 2007 Dec;81(24):13631-9
17913808
J Biol Chem. 1984 Dec 10;259(23):14835-9
6501319
J Virol. 2006 Apr;80(8):4191-5
16571837
Biochem Biophys Res Commun. 2005 Oct 14;336(1):61-8
16122702
Nat Rev Immunol. 2008 Jul;8(7):559-68
18575461
J Biochem. 2005 Dec;138(6):711-9
16428300
Curr Top Microbiol Immunol. 2007;316:233-50
17969451
J Biol Chem. 2005 Jul 22;280(29):27004-12
15908698
J Biol Chem. 2008 Apr 4;283(14):8783-7
18287095
Cytokine Growth Factor Rev. 2006 Dec;17(6):411-21
17097911
J Virol. 2009 Feb;83(4):1602-10
19073728
Biochem Biophys Res Commun. 2003 Aug 1;307(3):431-4
12893238
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1440-5
16434471
J Virol. 1998 Apr;72(4):2962-8
9525617
Protein Sci. 2008 Jun;17(6):1035-43
18424514
J Virol. 2004 Dec;78(24):13943-53
15564502
J Biol Chem. 1986 Jul 5;261(19):8811-6
3087979
Mol Cell Biol. 2005 Aug;25(15):6338-45
16024773
Cell Host Microbe. 2007 Dec 13;2(6):404-16
18078692
J Biol Chem. 2006 Feb 17;281(7):3989-94
16352599
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13069-74
11087861
J Virol. 2002 Mar;76(6):3038-44
11861870
Annu Rev Cell Dev Biol. 2006;22:159-80
16753028
Virology. 1976 Apr;70(2):324-38
57667
J Interferon Cytokine Res. 1996 Nov;16(11):919-27
8938567
J Cell Biol. 2005 Jan 3;168(1):89-101
15623582
J Virol. 2006 Jul;80(13):6267-75
16775314
J Virol. 2004 Jun;78(12):6636-48
15163754
BMC Biochem. 2008 Oct 21;9 Suppl 1:S7
19007437
Semin Cell Dev Biol. 2004 Apr;15(2):237-46
15209384
J Biol Chem. 2002 Mar 22;277(12):9976-81
11788588
Cell Signal. 2007 Sep;19(9):1893-8
17532187
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20031-6
18056634
Virology. 2008 Jul 20;377(1):30-8
18555885
Methods Mol Biol. 2008;446:139-49
18373255
Cytokine. 2008 Sep;43(3):359-67
18707898
Mol Cell Biol. 2004 Nov;24(21):9592-600
15485925
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13057-62
11087859
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15690-5
18836078
Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1371-6
17227866
J Virol. 2001 Nov;75(22):10623-9
11602704
Expert Rev Anti Infect Ther. 2005 Feb;3(1):61-79
15757458
J Virol. 2004 Jun;78(11):5554-63
15140952
J Cell Physiol. 2009 Jan;218(1):175-82
18792916
EMBO Rep. 2002 Jul;3(7):636-40
12101095
J Virol. 2003 Feb;77(3):1812-9
12525615
Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):409-17
17689132
Virology. 1990 Jun;176(2):633-7
2161153
Proc Natl Acad Sci U S A. 2004 May 18;101(20):7578-82
15131269
Microbes Infect. 2004 Feb;6(2):150-6
14998512
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13871-6
11095724
J Virol. 2009 Jan;83(2):1147-51
19004958
Biochem Biophys Res Commun. 2005 Oct 14;336(1):9-13
16112642
Oncogene. 2004 Apr 1;23(14):2540-7
14676825
PLoS Pathog. 2008 Jul 04;4(7):e1000096
18604270
EMBO J. 2001 Feb 1;20(3):362-71
11157743
J Virol. 2008 May;82(10):4884-97
18321968
J Virol. 2008 May;82(10):4898-907
18321969
J Virol. 2003 Sep;77(18):9987-92
12941909
J Immunol. 2008 Nov 1;181(9):6467-72
18941237
Virology. 2008 Mar 15;372(2):221-32
18063004
Virology. 1977 Jun 1;79(1):1-13
194399
J Biol Chem. 1987 Aug 15;262(23):11315-23
2440890
Front Biosci. 2005 Sep 01;10:2701-22
15970528
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3974-9
18305167
Virol J. 2008 Oct 13;5:116
18851747
J Virol. 2003 Mar;77(6):3384-93
12610113
J Virol. 2007 Sep;81(17):9193-201
17609272
Sci STKE. 2004 Aug 03;2004(245):pe43
15304665
J Cell Sci. 2004 May 1;117(Pt 11):2357-67
15126635
J Virol. 2003 Sep;77(17):9474-85
12915562
J Interferon Cytokine Res. 2004 Jan;24(1):1-19
14980080
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13063-8
11087860
J Mol Biol. 2003 Feb 14;326(2):493-502
12559917
J Virol. 2007 Sep;81(18):9769-77
17609263
Circ Res. 2007 May 11;100(9):1276-91
17495234