Mice Lacking the ISG15 E1 Enzyme UbE1L Demonstrate Increased Susceptibility to Both Mouse-adapted and Non-mouse-adapted Influenza B Virus Infection

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2008 Nov 14

PMID 19004958

Citations 77

Authors

Caroline Lai

Jessica J Struckhoff

Jana Schneider

Luis Martinez-Sobrido

Thorsten Wolff

Adolfo Garcia-Sastre

Dong-Er Zhang

Deborah J Lenschow

Affiliations

Soon will be listed here.

Abstract

ISG15 functions as a critical antiviral molecule against influenza virus, with infection inducing both the conjugation of ISG15 to target proteins and production of free ISG15. Here, we report that mice lacking the ISG15 E1 enzyme UbE1L fail to form ISG15 conjugates. Both UbE1L(-/-) and ISG15(-/-) mice display increased susceptibility to influenza B virus infection, including non-mouse-adapted strains. Finally, we demonstrate that ISG15 controls influenza B virus infection through its action within radioresistant stromal cells and not bone marrow-derived cells. Thus, the conjugation of ISG15 to target proteins within stromal cells is critical to its activity against influenza virus.

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References

DCunha J, Ramanujam S, WAGNER R, Witt P, KNIGHT Jr E, Borden E . In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol. 1996; 157(9):4100-8. View

Shornick L, Wells A, Zhang Y, Patel A, Huang G, Takami K . Airway epithelial versus immune cell Stat1 function for innate defense against respiratory viral infection. J Immunol. 2008; 180(5):3319-28. DOI: 10.4049/jimmunol.180.5.3319. View

Zhao C, Denison C, Huibregtse J, Gygi S, Krug R . Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci U S A. 2005; 102(29):10200-5. PMC: 1177427. DOI: 10.1073/pnas.0504754102. View

Okumura F, Zou W, Zhang D . ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP. Genes Dev. 2007; 21(3):255-60. PMC: 1785121. DOI: 10.1101/gad.1521607. View

Okumura A, Lu G, Pitha-Rowe I, Pitha P . Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15. Proc Natl Acad Sci U S A. 2006; 103(5):1440-5. PMC: 1360585. DOI: 10.1073/pnas.0510518103. View

Kim K, Yan M, Malakhova O, Luo J, Shen M, Zou W . Ube1L and protein ISGylation are not essential for alpha/beta interferon signaling. Mol Cell Biol. 2005; 26(2):472-9. PMC: 1346917. DOI: 10.1128/MCB.26.2.472-479.2006. View

Malakhov M, Malakhova O, Kim K, Ritchie K, Zhang D . UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J Biol Chem. 2002; 277(12):9976-81. DOI: 10.1074/jbc.M109078200. View

Kim K, Giannakopoulos N, Virgin H, Zhang D . Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation. Mol Cell Biol. 2004; 24(21):9592-600. PMC: 522249. DOI: 10.1128/MCB.24.21.9592-9600.2004. View

Lenschow D, Lai C, Frias-Staheli N, Giannakopoulos N, Lutz A, Wolff T . IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci U S A. 2007; 104(4):1371-6. PMC: 1783119. DOI: 10.1073/pnas.0607038104. View

10.

Wang F, Ma Y, Barrett J, Gao X, Loh J, Barton E . Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. Nat Immunol. 2004; 5(12):1266-74. DOI: 10.1038/ni1132. View

11.

Giannakopoulos N, Luo J, Papov V, Zou W, Lenschow D, Jacobs B . Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun. 2005; 336(2):496-506. DOI: 10.1016/j.bbrc.2005.08.132. View

12.

Okumura A, Pitha P, Harty R . ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. Proc Natl Acad Sci U S A. 2008; 105(10):3974-9. PMC: 2268823. DOI: 10.1073/pnas.0710629105. View

13.

DCunha J, KNIGHT Jr E, Haas A, Truitt R, Borden E . Immunoregulatory properties of ISG15, an interferon-induced cytokine. Proc Natl Acad Sci U S A. 1996; 93(1):211-5. PMC: 40208. DOI: 10.1073/pnas.93.1.211. View

14.

Owhashi M, Taoka Y, Ishii K, Nakazawa S, Uemura H, Kambara H . Identification of a ubiquitin family protein as a novel neutrophil chemotactic factor. Biochem Biophys Res Commun. 2003; 309(3):533-9. DOI: 10.1016/j.bbrc.2003.08.038. View

15.

Lenschow D, Giannakopoulos N, Gunn L, Johnston C, OGuin A, Schmidt R . Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol. 2005; 79(22):13974-83. PMC: 1280211. DOI: 10.1128/JVI.79.22.13974-13983.2005. View

16.

Recht M, Borden E, KNIGHT Jr E . A human 15-kDa IFN-induced protein induces the secretion of IFN-gamma. J Immunol. 1991; 147(8):2617-23. View

17.

Wong J, Pung Y, Sze N, Chin K . HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc Natl Acad Sci U S A. 2006; 103(28):10735-40. PMC: 1484417. DOI: 10.1073/pnas.0600397103. View

18.

Samuel C . Antiviral actions of interferons. Clin Microbiol Rev. 2001; 14(4):778-809, table of contents. PMC: 89003. DOI: 10.1128/CMR.14.4.778-809.2001. View

19.

Malakhova O, Zhang D . ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response. J Biol Chem. 2008; 283(14):8783-7. PMC: 2276364. DOI: 10.1074/jbc.C800030200. View

20.

Donelan N, Dauber B, Wang X, Basler C, Wolff T, Garcia-Sastre A . The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation. J Virol. 2004; 78(21):11574-82. PMC: 523269. DOI: 10.1128/JVI.78.21.11574-11582.2004. View