Key result
Exposure of Equine Rhinitis A Virus to mildly acidic pH induces the transient formation of empty 80S particles prior to dissociation into pentamers, suggesting a unified mechanism of picornavirus cell entry.
The identification of a transient empty 80S particle intermediate during ERAV acid-induced dissociation suggests a unified mechanism for picornavirus cell entry.
May guide antiviral development targeting picornavirus entry; leaves open applicability to human pathogens.
Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses introduce their RNA genome into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope to facilitate fusion with cellular membranes. It has been thought that the dissociation of the FMDV particle into pentameric subunits at acidic pH is the mechanism for genome release during cell entry, but this raises the problem of how transfer across the endosome membrane of the genome might be facilitated. In contrast, most other picornaviruses form 'altered' particle intermediates (not reported for aphthoviruses) thought to induce membrane pores through which the genome can be transferred. Here we show that ERAV, like FMDV, dissociates into pentamers at mildly acidic pH but demonstrate that dissociation is preceded by the transient formation of empty 80S particles which have released their genome and may represent novel biologically relevant intermediates in the aphthovirus cell entry process. The crystal structures of the native ERAV virus and a low pH form have been determined via highly efficient crystallization and data collection strategies, required due to low virus yields. ERAV is closely similar to FMDV for VP2, VP3 and part of VP4 but VP1 diverges, to give a particle with a pitted surface, as seen in cardioviruses. The low pH particle has internal structure consistent with it representing a pre-dissociation cell entry intermediate. These results suggest a unified mechanism of picornavirus cell entry.
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Tuthill et al. (2009) studied Equine Rhinitis A Virus (ERAV) infection. Low pH exposure vs. Neutral pH was evaluated on Viral capsid structure and dissociation. Exposure of Equine Rhinitis A Virus to mildly acidic pH induces the transient formation of empty 80S particles prior to dissociation into pentamers, suggesting a unified mechanism of picornavirus cell entry.
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