A new role for ns polyprotein cleavage in Sindbis virus replication.

Journal of Virology
Rodion GorchakovIlya Frolov

Abstract

One of the distinguishing features of the alphaviruses is a sequential processing of the nonstructural polyproteins P1234 and P123. In the early stages of the infection, the complex of P123+nsP4 forms the primary replication complexes (RCs) that function in negative-strand RNA synthesis. The following processing steps make nsP1+P23+nsP4, and later nsP1+nsP2+nsP3+nsP4. The latter mature complex is active in positive-strand RNA synthesis but can no longer produce negative strands. However, the regulation of negative- and positive-strand RNA synthesis apparently is not the only function of ns polyprotein processing. In this study, we developed Sindbis virus mutants that were incapable of either P23 or P123 cleavage. Both mutants replicated in BHK-21 cells to levels comparable to those of the cleavage-competent virus. They continuously produced negative-strand RNA, but its synthesis was blocked by the translation inhibitor cycloheximide. Thus, after negative-strand synthesis, the ns proteins appeared to irreversibly change conformation and formed mature RCs, in spite of the lack of ns polyprotein cleavage. However, in the cells having no defects in alpha/beta interferon (IFN-alpha/beta) production and signaling, the cleavage-defici...Continue Reading

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Citations

May 25, 2012·Journal of Virology·Svetlana AtashevaIlya Frolov
Aug 8, 2008·Journal of Virology·Rodion GorchakovIlya Frolov
Sep 10, 2010·Journal of Virology·Elena I FrolovaIlya Frolov
Dec 18, 2009·Journal of Virology·Margus VarjakAndres Merits
Jan 21, 2011·Journal of Virology·Jonathan C RuppRichard W Hardy
Apr 12, 2012·Journal of Virology·Jason D MatthewsTeryl K Frey
Feb 22, 2012·Journal of Virology·Ilya FrolovElena I Frolova
Jan 30, 2013·PLoS Neglected Tropical Diseases·Kali D Saxton-ShawAnn M Powers
Sep 3, 2009·Future Microbiology·Joyce JoseRichard J Kuhn
Jul 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dal Young KimIlya Frolov
Apr 6, 2012·Virus Research·Christine PampenoDaniel Meruelo
Jul 30, 2015·The Journal of General Virology·Jonathan C RuppRichard W Hardy
Feb 10, 2018·Viruses·Farhana Abu Bakar, Lisa F P Ng
Nov 1, 2016·Antimicrobial Agents and Chemotherapy·Pratyush Kumar DasMati Karelson
Jan 17, 2014·Journal of Virology·Kristina A Stoermer BurrackThomas E Morrison
Aug 25, 2012·Uirusu·Yoshio MoriKiyoko Okamoto
Oct 22, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Anthony M MarcheseMichael D Robek

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