ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells.

Proceedings of the National Academy of Sciences of the United States of America
Chen ZhaoRobert M Krug

Abstract

ISG15 is an IFN-alpha/beta-induced, ubiquitin-like protein that is conjugated to a wide array of cellular proteins through the sequential action of three conjugation enzymes that are also induced by IFN-alpha/beta. Recent studies showed that ISG15 and/or its conjugates play an important role in protecting cells from infection by several viruses, including influenza A virus. However, the mechanism by which ISG15 modification exerts antiviral activity has not been established. Here we extend the repertoire of ISG15 targets to a viral protein by demonstrating that the NS1 protein of influenza A virus (NS1A protein), an essential, multifunctional protein, is ISG15 modified in virus-infected cells. We demonstrate that the major ISG15 acceptor site in the NS1A protein in infected cells is a critical lysine residue (K41) in the N-terminal RNA-binding domain (RBD). ISG15 modification of K41 disrupts the association of the NS1A RBD domain with importin-alpha, the protein that mediates nuclear import of the NS1A protein, whereas the RBD retains its double-stranded RNA-binding activity. Most significantly, we show that ISG15 modification of K41 inhibits influenza A virus replication and thus contributes to the antiviral action of IFN-beta...Continue Reading

References

Dec 1, 1992·The Journal of General Virology·E Hatada, R Fukuda
May 8, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chen ZhaoRobert M Krug
Oct 16, 2004·Molecular and Cellular Biology·Keun Il KimDong-Er Zhang
Apr 6, 2005·Molecular Cell·Ronald T Hay
Oct 28, 2005·Essays in Biochemistry·Helen C Ardley, Philip A Robinson
Jan 13, 2006·The Journal of Biological Chemistry·Anahita DasturJon M Huibregtse
Jan 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Atsushi OkumuraPaula M Pitha
Apr 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ji-Young Min, Robert M Krug
Jul 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Joyce Jing Yi WongKeh-Chuang Chin
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Deborah J LenschowHerbert Whiting Virgin
Feb 10, 2007·Genes & Development·Fumihiko OkumuraDong-Er Zhang
Feb 22, 2008·The Journal of Biological Chemistry·Oxana A Malakhova, Dong-Er Zhang
Feb 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Atsushi OkumuraRonald N Harty
Sep 18, 2008·The Journal of General Virology·Benjamin G HaleDavid Jackson
Dec 17, 2008·Journal of Virology·Nadia V GiannakopoulosHerbert Whiting Virgin

❮ Previous
Next ❯

Citations

Jan 31, 2013·Journal of Medicinal Chemistry·Sara R da SilvaPatrick T Gunning
Sep 12, 2012·Cell Research·Jun-Bao Fan, Dong-Er Zhang
Aug 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rongjin GuanGaetano T Montelione
Dec 31, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Dongxian Zhang, Dong-Er Zhang
Sep 10, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jessica A Campbell, Deborah J Lenschow
Aug 13, 2010·Journal of Virology·Kevin M CoombsEarl G Brown
Nov 5, 2010·Journal of Virology·Ke XuBing Sun
Mar 12, 2010·Journal of Virology·Gijs A VersteegAdolfo García-Sastre
Oct 4, 2013·BMC Systems Biology·Yukiko MatsuokaYoshihiro Kawaoka
Jun 14, 2012·PloS One·Veronika N BadeGerrit J K Praefcke
Oct 19, 2013·PLoS Pathogens·Emilio YángüezSusana Guerra
Aug 24, 2010·Future Virology·Yuliang Liu, Ronald N Harty
Nov 2, 2013·Bioinformatics·Xiangtian YuLuonan Chen
Mar 13, 2012·Annual Review of Biochemistry·Annemarthe G van der Veen, Hidde L Ploegh
Nov 19, 2011·Expert Opinion on Investigational Drugs·Jia LiuDian-zheng Zhang
Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Lars KetscherKlaus-Peter Knobeloch
Oct 11, 2015·Virus Research·Elena Carnero, Puri Fortes
Oct 8, 2013·Journal of Molecular Biology·David J Morales, Deborah J Lenschow
Jan 24, 2016·Cellular and Molecular Life Sciences : CMLS·Susana Sánchez-TenaJose Luis Rosa
Feb 19, 2013·Trends in Microbiology·Chen ZhaoRobert M Krug
Dec 27, 2011·Trends in Pharmacological Sciences·Konstantin H MüllerDenis E Kainov
Nov 22, 2011·Biochemical and Biophysical Research Communications·Punsiri M ColonneSanjeev K Sahni
Dec 6, 2011·Biochemical and Biophysical Research Communications·Lars KetscherKlaus-Peter Knobeloch
Oct 27, 2011·Virus Research·Adolfo García-Sastre
Feb 15, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hans D KlenkMikhail Matrosovich
Aug 12, 2010·Current Opinion in Microbiology·Kasinath ViswanathanVictor DeFilippis
Sep 4, 2014·The Journal of General Virology·Daniel Marc

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.