Structures of three infection cycle intermediates of Coxsackievirus A6

Carina R Büttner, Radovan Spurny, Tibor Füzik, Pavel Plevka

CEITEC-MU, Structural Biology, Masaryk University, Brno
corresponding author: carina.buttner@ceitec.muni.cz

Coxsackievirus A6 (CVA6) has recently overtaken CVA16 and Enterovirus 71 as the primary causative agent of epidemics of hand, foot and mouth disease (HFMD) that usually affects children but occasionally spreads also to adolescents and adults. Millions of self-limiting HFMD cases and several hundred of deaths are reported each year, predominantly in the Asian-Pacific region. However, no vaccine against CVA6 is available, and vaccine development against CVA16 and EV71 has proven challenging and even trivalent vaccine candidates fail to cross-protect. Recently published structural characterizations of CVA6 [1,2] lack structural data of the native antigenic, mature virion. Unlike other picornaviruses, CVA6 virus particle preparations yield visibly only expanded and empty capsid conformations [1, and our observations]. By using a very large cryo-electron microscopy (cryo-EM) dataset, we were able to detect a small subset of mature virions during the 3D classification steps of single particle reconstruction. Here, we present high-resolution cryo-EM structures of CVA6 infection cycle intermediates, including mature virion, expanded and empty capsids to 3.3, 2.8 and 3.2 Å resolution (at FSC = 0.143), respectively. Structure comparisons, conformational changes and their implications will be discussed.

 

1.       Xu, L., et al., Nat Commun (2017) 8(1): 505.

2.       2. Chen, J., et al., J Virol (2018) 92(2): e01257-17.