Structures of Coxsackievirus A10 unveil the molecular mechanisms of receptor binding and viral uncoating.

Abstract

Coxsackievirus A10 (CVA10), a human type-A Enterovirus (HEV-A), can cause diseases ranging from hand-foot-and-mouth disease to polio-myelitis-like disease. CVA10, together with some other HEV-As, utilizing the molecule KREMEN1 as an entry receptor, constitutes a KREMEN1-dependent subgroup within HEV-As. Currently, there is no vaccine or antiviral therapy available for treating diseases caused by CVA10. The atomic-resolution structure of the CVA10 virion, which is within the KREMEN1-dependent subgroup, shows significant conformational differences in the putative receptor binding sites and serotype-specific epitopes, when compared to the SCARB2-dependent subgroup of HEV-A, such as EV71, highlighting specific differences between the sub-groups. We also report two expanded structures of CVA10, an empty particle and uncoating intermediate at atomic resolution, as well as a medium-resolution genome structure reconstructed using a symmetry-mismatch method. Structural comparisons coupled with previous results, reveal an ordered signal transmission process for enterovirus uncoating, converting exo-genetic receptor-attachment inputs into a generic RNA release mechanism.

• Authors: Ling Zhu, Yao Sun, Jinyan Fan, Bin Zhu, Lei Cao, Qiang Gao, Yanjun Zhang, Hongrong Liu, Zihe Rao, Xiangxi Wang
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 4985 (11 26 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 30478256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Virus

Topics

• Animals
• Capsid (metabolism)
• Cryoelectron Microscopy
• Enterovirus (chemistry, ultrastructure)
• Enterovirus Infections (pathology, virology)
• Genome, Viral
• Mice
• Models, Molecular
• Receptors, Virus (metabolism)
• Virus Uncoating