Poliovirus 2A(Pro) increases viral mRNA and polysome stability coordinately in time with cleavage of eIF4G.

Journal of Virology
Brian J Kempf, David J Barton

Abstract

Poliovirus (PV) 2A protease (2A(Pro)) cleaves eukaryotic initiation factors 4GI and 4GII (eIF4GI and eIF4GII) within virus-infected cells, effectively halting cap-dependent mRNA translation. PV mRNA, which does not possess a 5' cap, is translated via cap-independent mechanisms within viral protease-modified messenger ribonucleoprotein (mRNP) complexes. In this study, we determined that 2A(Pro) activity was required for viral polysome formation and stability. 2A(Pro) cleaved eIF4GI and eIF4GII as PV polysomes assembled. A 2A(Cys109Ser) (2A(Pro) with a Cys109Ser mutation) protease active site mutation that prevented cleavage of eIF4G coordinately inhibited the de novo formation of viral polysomes, the stability of viral polysomes, and the stability of PV mRNA within polysomes. 2A(Cys109Ser)-associated defects in PV mRNA and polysome stability correlated with defects in PV mRNA translation. 3C(Pro) activity was not required for viral polysome formation or stability. 2A(Pro)-mediated cleavage of eIF4G along with poly(rC) binding protein binding to the 5' terminus of uncapped PV mRNA appear to be concerted mechanisms that allow PV mRNA to form mRNP complexes that evade cellular mRNA degradation machinery.

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Citations

May 8, 2009·Journal of Virology·Lyudmila I RomanovaVadim I Agol
Feb 13, 2009·Journal of Virology·Juliet M Morrison, Vincent R Racaniello
Aug 5, 2010·Journal of Biomedical Science·Chee-Hing YangShih-Yen Lo
Aug 12, 2008·Virus Research·Olga Fernández-MiragallEncarnación Martínez-Salas
Dec 22, 2010·Acta Biochimica Et Biophysica Sinica·Wenwu TianXianEn Zhang
Apr 1, 2017·Frontiers in Cellular and Infection Microbiology·Haoyu DengHonglin Luo
Aug 9, 2017·Frontiers in Microbiology·Xiaoyao YangXiaoyue Chen
Sep 13, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiangle ZhangHaixue Zheng
Jan 22, 2011·Virology·Ross E RhoadesRalph Feuer

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