A research report published in the Journal of Nature Communications reveals the full-particle atomic resolution structure of the three different life cycles of the hand-foot-and-mouth virus Coxsackie A10 (CVA10) and the medium-resolution genomic structure of the capsid intermediate completed by the researcher in the Institute of Biophysics, Chinese Academy of Sciences, which is another important research result after they completed the study of the full-particle structure and function of the different life cycles of the opponent’s foot-foot virus EV71 and CVA16.

 

EV71 and CVA16 have been the main pathogens causing hand, foot, and mouth disease, and EV71 vaccine can only protect hand, foot and mouth disease caused by EV71 infection, but not cross-protection of hand, foot and mouth disease caused by other virus infections. And with the vaccination of EV71 vaccine and possible genetic recombination events between enteroviruses, the prevalence of hand, foot and mouth virus is different now.

 

 

In recent years, cases of hand, foot, and mouth caused by CVA10 infection have increased significantly, and sick children may also develop more serious clinical symptoms such as aseptic meningitis. However, there is currently no CVA10 vaccine marketed and antiviral treatment methods and methods for CVA10, which makes it necessary to carry out structural and functional studies on CVA10.

 

CVA10 belongs to the small RNA virus family of enteroviruses which consists of a large group of viruses with a diameter of about 30 nm, a single-stranded positive-stranded RNA wrapped in a capsid, and a non-encapsulated, icosahedral structure. The researchers isolated three different life cycle whole virus particles of CVA10, and obtained the atomic resolution structure of the three particles by cryo-electron microscopy. The structure of CVA10 solid particles is similar to that of other enteroviruses. However, in the potential receptor binding regions and neutralizing antibody binding regions, CVA10 has a large difference in structure and surface potential distribution from EV71 and CVA16.

 

The researchers compared the three particle structures of CVA10 and found that the diameter of the hollow particles and the shelling intermediate particles is about 5% larger than that of the solid particles, and the major channel and the off-axis channel are formed at the secondary axis of the icosahedron of the hollow particles. The intermediate axis of the intermediate has only the major channel, and the off-axis channel is filled by the capsid proteins VP1 and VP2. In addition, according to the structural comparison, it was found that the rotation of the primary polymer unit and the displacement of the internal components occurred in the three kinds of particles, and the hollow particles produced a multi-site disorder with respect to the solid particles and the intermediate particles.

 

The results of immunogenicity evaluation showed that the solid particles and intermediate particles were much more immunogenic than the hollow particles, which was consistent with the structural analysis of the researchers, and is considered a good inspiration for the development of hand, foot and mouth vaccine. The researchers also obtained the medium-resolution nucleic acid structure of the capsid intermediate by a symmetry-mismatch method, determined the key sites of interaction between the several capsids and nucleic acids, and explained the dynamic process of releasing nucleic acid from the enterovirus capsid.

 

 

Reference

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Zhu, L. et al. Mbio 2018