The Dynamic Capsid Structures of the Noroviruses.

Hong Smith,Thomas Smith

doi:10.3390/v11030235

Abstract

Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. New strains evolve every 2–4 years by escaping herd immunity and cause worldwide epidemics. In the US alone, noroviruses are responsible for ~20 million cases and more than 70,000 hospitalizations of infected children, annually. Efforts towards a vaccine have been hindered by a lack of detailed structural information about antibody binding and the mechanisms of antibody escape. Caliciviruses have 180 copies of the major capsid protein (VP1; ~58 kDa), that is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. The P domain is subdivided into P1 and P2 subdomains, with the latter containing the binding sites for cellular receptors and neutralizing antibodies. There is increasing evidence that these viruses are extremely dynamic and this flexibility is critical for viral replication. There are at least two modes of flexibility; the entire P domain relative to the shell and within the P domain itself. Here, the details and possible roles for this remarkable flexibility will be reviewed.

Highlights

Noroviruses are the major cause of epidemic gastroenteritis in humans and, as such, are important pathogens, causing ~20 million cases annually, resulting in more than 70,000 hospitalizations and 570–800 deaths in the US alone
As with MNV and rabbit hemorrhagic disease virus (RHDV), the P domain appeared as a second outer shell, and a half-section through the virus like particle (VLP) revealed that the P domain was raised off the S domain by ~15 Å
As will be discussed below, there are very recent results that show that flexibility within the P domain may help human noroviruses bind to the histo-blood group antigens (HBGA) [28]

Summary

Introduction

Noroviruses are the major cause of epidemic gastroenteritis in humans and, as such, are important pathogens (for review, see [1]), causing ~20 million cases annually, resulting in more than 70,000 hospitalizations and 570–800 deaths in the US alone. Efforts to make effective norovirus vaccines have been thwarted by our lack of understanding of the structural mechanisms of viral escape. Developing efficacious vaccines requires a detailed understanding of how escape mutations block antibody binding and the limitations in altering the virus capsid to evade the immune system. Such studies have been difficult with human noroviruses. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. We show the entire capsid of mouse.

54 The purpose

Interaction between Human Noroviruses and Polysaccharides

Feline Calicivirus Interactions with Its Receptor

MNV P Domain Flexibility and Antibody Escape

Overview of Structural Studies

Summary