Structural basis for suppression of a host antiviral response by influenza A virus.

Proceedings of the National Academy of Sciences of the United States of America
Kalyan DasGaetano T Montelione

Abstract

Influenza A viruses are responsible for seasonal epidemics and high mortality pandemics. A major function of the viral NS1A protein, a virulence factor, is the inhibition of the production of IFN-beta mRNA and other antiviral mRNAs. The NS1A protein of the human influenza A/Udorn/72 (Ud) virus inhibits the production of these antiviral mRNAs by binding the cellular 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), which is required for the 3' end processing of all cellular pre-mRNAs. Here we report the 1.95-A resolution X-ray crystal structure of the complex formed between the second and third zinc finger domain (F2F3) of CPSF30 and the C-terminal domain of the Ud NS1A protein. The complex is a tetramer, in which each of two F2F3 molecules wraps around two NS1A effector domains that interact with each other head-to-head. This structure identifies a CPSF30 binding pocket on NS1A comprised of amino acid residues that are highly conserved among human influenza A viruses. Single amino acid changes within this binding pocket eliminate CPSF30 binding, and a recombinant Ud virus expressing an NS1A protein with such a substitution is attenuated and does not inhibit IFN-beta pre-mRNA processing. This bindin...Continue Reading

References

Jan 1, 1992·The Journal of General Virology·E HatadaR Fukuda
Nov 14, 1997·Nature Structural Biology·C Y ChienG T Montelione
Mar 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·J TalonP Palese
Apr 25, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·T IwamuraT Fujita
Apr 5, 2002·Journal of Virology·Lois A ZitzowJacqueline M Katz
Jul 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mee-Jung KimRobert M Krug
Feb 26, 2004·Nature Structural & Molecular Biology·Brian P HudsonPeter E Wright
Apr 6, 2005·Methods in Enzymology·Thomas B ActonGaetano T Montelione
Aug 3, 2005·Nature Reviews. Microbiology·Taisuke Horimoto, Yoshihiro Kawaoka
Jan 3, 2006·Advances in Virus Research·Diana L Noah, Robert M Krug
Apr 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ji-Young Min, Robert M Krug
May 23, 2006·Nature Structural & Molecular Biology·Zachary A Bornholdt, B V Venkataram Prasad
Sep 12, 2006·Proceedings of the National Academy of Sciences of the United States of America·Benjamin G HaleRichard E Randall
Apr 20, 2007·Journal of Virology·Georg KochsLuis Martínez-Sobrido
Jul 1, 2008·Virology·Benjamin G HaleRupert J Russell

❮ Previous
Next ❯

Citations

May 28, 2009·Science in China. Series C, Life Sciences·Yingfang LiuZihe Rao
Jun 26, 2013·Antiviral Research·Daniel A Engel
May 23, 2012·Journal of Medicinal Chemistry·Kalyan Das
Mar 16, 2012·Nature·Ivan MarazziAlexander Tarakhovsky
Apr 13, 2010·Nature Structural & Molecular Biology·Kalyan DasEddy Arnold
Sep 29, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Jamie L MichalekSarah L J Michel
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Benjamin G HaleRupert J Russell
May 31, 2011·The Journal of Biological Chemistry·James M AraminiGaetano T Montelione
Aug 28, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thorsten Wolff, Stephan Ludwig
Jan 21, 2009·Acta Crystallographica. Section D, Biological Crystallography·Shuangluo XiaJon D Robertus
Aug 9, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Philip S KerryRupert J M Russell
May 7, 2010·Journal of Virology·Benjamin G HaleAdolfo García-Sastre
Dec 22, 2009·Future Microbiology·Benjamin G HaleAdolfo García-Sastre
Nov 22, 2012·Viruses·Carolien E van de SandtGuus F Rimmelzwaan
Jan 25, 2013·Viruses·Irene Ramos, Ana Fernandez-Sesma
Jun 19, 2012·Drug Discovery Today·Juan DuHuan-Xiang Zhou
Dec 27, 2011·Trends in Pharmacological Sciences·Konstantin H MüllerDenis E Kainov
Oct 27, 2011·Virus Research·Adolfo García-Sastre
Nov 26, 2010·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Vernon J LeeMartin L Hibberd
Aug 9, 2011·Wiley Interdisciplinary Reviews. RNA·Qin Yang, Sylvie Doublié
Jun 15, 2014·The Journal of General Virology·Benjamin G Hale

❮ 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.