Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of ebola virus

Journal of Virology
Amy L HartmanStuart T Nichol

Abstract

Zaire ebolavirus causes a rapidly progressing hemorrhagic disease with high mortality. Identification of the viral virulence factors that contribute to the severity of disease induced by Ebola virus is critical for the design of therapeutics and vaccines against the disease. Given the rapidity of disease progression, virus interaction with the innate immune system early in the course of infection likely plays an important role in determining the outcome of the disease. The Ebola virus VP35 protein inhibits the activation of IRF-3, a critical transcription factor for the induction of early antiviral immunity. Previous studies revealed that a single amino acid change (R312A) in VP35 renders the protein unable to inhibit IRF-3 activation. A reverse-genetics-generated, mouse-adapted, recombinant Ebola virus that encodes the R312A mutation in VP35 was produced. We found that relative to the case for wild-type virus containing the authentic VP35 sequence, this single amino acid change in VP35 renders the virus completely attenuated in mice. Given that these viruses differ by only a single amino acid in the IRF-3 inhibitory domain of VP35, the level of alteration of virulence is remarkable and highlights the importance of VP35 for the...Continue Reading

References

Sep 5, 1998·The Journal of Infectious Diseases·M BrayJ Huggins
Feb 13, 1999·The Journal of Infectious Diseases·T G KsiazekC J Peters
Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·C F BaslerP Palese
Jun 28, 2003·Journal of Virology·Christopher F BaslerAdolfo García-Sastre
Dec 25, 2003·Journal of Virology·Manisha GuptaPierre E Rollin
Nov 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·J AndrejevaR E Randall
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Manisha GuptaPierre E Rollin
Sep 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gunhild UnterstabThorsten Wolff
May 13, 2006·Science·Adolfo García-Sastre, Christine A Biron
May 16, 2006·Journal of Virology·St Patrick ReidChristopher F Basler
Jul 20, 2006·PLoS Pathogens·Hideki EbiharaYoshihiro Kawaoka
Aug 26, 2006·Nature Reviews. Immunology·Kenya Honda, Tadatsugu Taniguchi
Jun 26, 2007·Nature Reviews. Immunology·Mansour MohamadzadehAlan L Schmaljohn
Jun 26, 2007·PLoS Pathogens·Joost HaasnootBen Berkhout
Dec 6, 2007·The Journal of Infectious Diseases·Jonathan S TownerStuart T Nichol

❮ Previous
Next ❯

Citations

Feb 15, 2011·Biological Trace Element Research·Michalann Harthill
Jul 9, 2013·Trends in Microbiology·Jason Mercer, Urs F Greber
Jan 19, 2010·Nature Structural & Molecular Biology·Daisy W LeungGaya K Amarasinghe
Jan 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daisy W LeungGaya K Amarasinghe
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christopher R KimberlinErica Ollmann Saphire
Nov 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Parameshwaran RamananGaya K Amarasinghe
Oct 19, 2011·The Journal of Infectious Diseases·Lawrence W LeungChristopher F Basler
Oct 19, 2011·The Journal of Infectious Diseases·Reed S ShabmanChristopher F Basler
Oct 10, 2012·The Journal of Infectious Diseases·Hideki EbiharaHeinz Feldmann
Feb 6, 2009·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Daisy W LeungGaya K Amarasinghe
May 1, 2009·Journal of Virology·Toru KubotaKeiko Ozato
Jun 12, 2009·Journal of Virology·Michael SchümannElke Mühlberger
Nov 6, 2009·Journal of Virology·Mathieu MateoViktor E Volchkov
Sep 3, 2011·Microbiology and Molecular Biology Reviews : MMBR·Denis Gerlier, Douglas S Lyles
Oct 14, 2011·Viruses·Steven B Bradfute, Sina Bavari
Jun 7, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Robert M Krug
Jul 10, 2010·Journal of Biomedicine & Biotechnology·Gavin C Bowick, Alan D T Barrett
Feb 16, 2016·Cell Reports·Megan R EdwardsChristopher F Basler
Feb 23, 2012·Antiviral Research·Travis K WarrenSina Bavari
Feb 16, 2012·Antiviral Research·Osvaldo MartinezChristopher F Basler
Nov 25, 2014·Cell·John Misasi, Nancy J Sullivan
Oct 7, 2015·Nature Reviews. Microbiology·Ilhem MessaoudiChristopher F Basler
Jun 12, 2010·Current Opinion in Microbiology·Gijs A Versteeg, Adolfo García-Sastre
Jul 15, 2015·Current Opinion in Immunology·Ilhem Messaoudi, Christopher F Basler
Feb 18, 2010·Biochimie·Imen Najjar, Remi Fagard
May 24, 2016·Environmental Science & Technology Letters·Mari Titcombe LeeLinsey C Marr
Apr 20, 2010·Journal of Molecular Biology·Daisy W LeungGaya K Amarasinghe

❮ 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.