Key result
Poliovirus 2A protease activity is required for viral polysome formation and stability, coordinating viral mRNA stability with the cleavage of eIF4G.
Poliovirus 2A protease activity is required for viral polysome formation and stability, allowing viral mRNA to evade cellular degradation machinery.
Should not change polio management; leaves open 2A protease as a potential antiviral target in enteroviruses.
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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Kempf et al. (2008) studied Poliovirus infection. Poliovirus 2APro mutation (2ACys109Ser) vs. Wild-type Poliovirus mRNA was evaluated on Viral mRNA and polysome stability. Poliovirus 2A protease activity is required for viral polysome formation and stability, coordinating viral mRNA stability with the cleavage of eIF4G.
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