A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes.

Journal of Virology
Kelly E Du PontBrian J Geiss

Abstract

The unwinding of double-stranded RNA intermediates is critical for the replication and packaging of flavivirus RNA genomes. This unwinding activity is achieved by the ATP-dependent nonstructural protein 3 (NS3) helicase. In previous studies, we investigated the mechanism of energy transduction between the ATP and RNA binding pockets using molecular dynamics simulations and enzymatic characterization. Our data corroborated the hypothesis that motif V is a communication hub for this energy transduction. More specifically, mutations T407A and S411A in motif V exhibit a hyperactive helicase phenotype, leading to the regulation of translocation and unwinding during replication. However, the effect of these mutations on viral infection in cell culture and in vivo is not well understood. Here, we investigated the role of motif V in viral replication using West Nile virus (Kunjin subtype) T407A and S411A mutants (T407A and S411A Kunjin, respectively) in cell culture and in vivo We were able to recover S411A Kunjin but unable to recover T407A Kunjin. Our results indicated that S411A Kunjin decreased viral infection and increased cytopathogenicity in cell culture compared to wild-type (WT) Kunjin. Similarly, decreased infection rates in ...Continue Reading

References

Jan 23, 1992·Nature·R M Story, T A Steitz
Jan 1, 1990·Annual Review of Microbiology·T J ChambersC M Rice
Oct 1, 1989·The Journal of General Virology·L M FlynnJ S Mackenzie
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Oct 5, 2001·Emerging Infectious Diseases·J H ScherretR A Hall
Jan 1, 1961·Annual Review of Entomology·R W CHAMBERLAIN, W D SUDIA
Jul 23, 2004·The New England Journal of Medicine·Tom Solomon
May 18, 2006·Emerging Infectious Diseases·Michael P BuschSimone A Glynn
Dec 19, 2007·The Journal of Cell Biology·Jennifer Q KwongGiovanni Manfredi
Jul 16, 2008·BMC Microbiology·Ricardo F Mercado-CurielMaria de L Muñoz
Nov 15, 2008·The EMBO Journal·Dahai LuoJulien Lescar
Oct 28, 2009·Antiviral Research·Scott C Weaver, William K Reisen
May 12, 2010·Current Opinion in Structural Biology·Margaret E Fairman-WilliamsEckhard Jankowsky
Sep 2, 2010·Cell Research·Hongbiao HuangJinbao Liu
Nov 26, 2010·Apoptosis : an International Journal on Programmed Cell Death·Qingzhen Liu, Rollie J Clem
Nov 4, 2011·The American Journal of Tropical Medicine and Hygiene·Timothy J GrayBart J Currie
Dec 6, 2011·Biochemical and Biophysical Research Communications·Eloise MastrangeloMario Milani
Apr 21, 2012·Emerging Infectious Diseases·Melinda J FrostPeter D Kirkland
May 30, 2012·Epidemiology and Infection·L R PetersenM P Busch
Aug 17, 2012·The Journal of General Virology·Erica M KellyDoria F Bowers
Aug 10, 2013·Wiley Interdisciplinary Reviews. RNA·Bejan J Saeedi, Brian J Geiss
Feb 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Katelyn O'NeillRollie J Clem
Jul 18, 2015·Viruses·Alexander W E FranzRollie J Clem
Sep 12, 2015·Nucleic Acids Research·Andrea Pérez-VillaGiovanni Bussi
Oct 28, 2016·Current Opinion in Virology·Nathan D Grubaugh, Gregory D Ebel
Aug 15, 2017·Current Opinion in Insect Science·Alexander T Ciota
Aug 18, 2017·Wiley Interdisciplinary Reviews. RNA·Carolin BrandBrian J Geiss
Nov 23, 2017·Nucleic Acids Research·Crystall M D SwarbrickSubhash G Vasudevan
Jan 7, 2018·Trends in Parasitology·Claudia Rückert, Gregory D Ebel
Feb 6, 2018·Trends in Microbiology·Glady Hazitha SamuelKevin M Myles
Feb 13, 2018·Nature Reviews. Microbiology·Christopher J NeufeldtRalf Bartenschlager

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Sep 3, 2021·Wiley Interdisciplinary Reviews. RNA·Kelly E Du PontBrian J Geiss

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