The early communication stages between serine proteases and enterovirus capsids in the race for viral disintegration

Author:

Corre Marie-Hélène,Rey Benjamin,David Shannon C.,Torii ShotaroORCID,Chiappe Diego,Kohn TamarORCID

Abstract

SummaryEnteroviruses are human pathogens known to challenge water safety1,2. Among the microbial stressors found in water, bacterial serine proteases contribute to the control of enterovirus persistence3. However, the structural interactions accounting for the susceptibility of enteroviruses to proteases remains unexplained. Here, we describe the molecular mechanisms involved in the recruitment of serine proteases to viral capsids. Among the virus types used, coxsackievirus A9 (CVA9), but not CVB5 and echovirus 11 (E11), was inactivated by Subtilisin A in a host-independent manner, while Bovine Pancreatic Trypsin (BPT) only reduced CVA9 infectivity in a host-dependent manner. Predictive interaction models of each protease with capsid protomers indicate the main targets as internal disordered protein (IDP) segments exposed either on the 5-fold vertex (DE loop VP1) or at the 5/2-fold intersection (C-terminal end VP1) of viral capsids. We further show that a functional binding protease/capsid depends on both the strength and the evolution over time of protease-VP1 complexes, and lastly on the local adaptation of proteases on surrounding viral regions. Finally, we identified three residues on CVA9 capsid that trigger cleavage by Subtilisin A, one of which acts as a sensor residue contributing to enzyme recognition on the DE loop. Overall, this study describes an important biological mechanism involved in enteroviruses biocontrol.

Publisher

Cold Spring Harbor Laboratory

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