Cryo-EM Structure of a Novel Calicivirus, Tulane Virus

Guimei Yu,Wen Jiang,Dongsheng Zhang,Fei Guo,Ming Tan,Xi Jiang

doi:10.1371/journal.pone.0059817

Abstract

Tulane virus (TV) is a newly isolated cultivatable calicivirus that infects juvenile rhesus macaques. Here we report a 6.3 Å resolution cryo-electron microscopy structure of the TV virion. The TV virion is about 400 Å in diameter and consists of a T = 3 icosahedral protein capsid enclosing the RNA genome. 180 copies of the major capsid protein VP1 (∼57 KDa) are organized into two types of dimers A/B and C/C and form a thin, smooth shell studded with 90 dimeric protrusions. The overall capsid organization and the capsid protein fold of TV closely resemble that of other caliciviruses, especially of human Norwalk virus, the prototype human norovirus. These close structural similarities support TV as an attractive surrogate for the non-cultivatable human noroviruses. The most distinctive feature of TV is that its C/C dimers are in a highly flexible conformation with significantly reduced interactions between the shell (S) domain and the protruding (P) domain of VP1. A comparative structural analysis indicated that the P domains of TV C/C dimers were much more flexible than those of other caliciviruses. These observations, combined with previous studies on other caliciviruses, led us to hypothesize that the enhanced flexibility of C/C dimer P domains are likely required for efficient calicivirus-host cell interactions and the consequent uncoating and genome release. Residues in the S-P1 hinge between the S and P domain may play a critical role in the flexibility of P domains of C/C dimers.

Highlights

The virus family Caliciviridae consists of four major genera, Norovirus, Sapovirus, Vesivirus and Lagovirus
Tulane virus (TV) consisted of 90 dimers of the major capsid proteins (VP1), which were arranged on a T = 3 icosahedral lattice (Figure 1B)
These 90 dimers were divided into two classes, denoted as the A/B dimer and the C/C dimer following the conventional nomenclature for caliciviruses

Summary

Introduction

The virus family Caliciviridae consists of four major genera, Norovirus, Sapovirus, Vesivirus and Lagovirus. Since the first primate calicivirus structure was reported in 1994 [2], several virus-like particle (VLP) and virion structures of caliciviruses have been determined These include the X-ray crystallographic structures of recombinant Norwalk Virus (rNV) [3] from the Norovirus genus, a native San Miguel sea lion virus (SMSV) [4] and a feline calicivirus virion (FCV) [5] from Vesivirus genus, and cryo-electron microscopy (cryo-EM) structures of recombinant Grimsby virus [6], recombinant Parkville virus [6], Rabbit hemorrhagic disease virus (RHDV, both VLPs and virions) [7,8,9,10], murine norovirus (MNV) virion [9,11] and a genogroup II genotype 10 (GII.10) NoV VLP [12]. The surface P dimers are suggested to be responsible for viral-host interaction [13,14]

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Results

Discussion

Conclusion