The effect of proteolytic enzymes and pH on GII.4 norovirus, during both interactions and non-interaction with Histo-Blood Group Antigens

Manon Chassaing,Alexis De Rougemont,Gaël Belliot,Christophe Gantzer,Nicolas Boudaud,Maëlle Robin,Julie Loutreul,Didier Majou

doi:10.1038/s41598-020-74728-z

Abstract

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Histo-Blood Groups Antigens (HBGAs) have been described as attachment factors, promoting HuNoV infection. However, their role has not yet been elucidated. This study aims to evaluate the ability of HBGAs to protect HuNoVs against various factors naturally found in the human digestive system. The effects of acid pH and proteolytic enzymes (pepsin, trypsin, and chymotrypsin) on GII.4 virus-like particles (VLPs) and GII.4 HuNoVs were studied, both during interactions and non-interaction with HBGAs. The results showed that GII.4 VLPs and GII.4 HuNoVs behaved differently following the treatments. GII.4 VLPs were disrupted at a pH of less than 2.0 and in the presence of proteolytic enzymes (1,500 units/mL pepsin, 100 mg/mL trypsin, and 100 mg/mL chymotrypsin). VLPs were also partially damaged by lower concentrations of trypsin and chymotrypsin (0.1 mg/mL). Conversely, the capsids of GII.4 HuNoVs were not compromised by such treatments, since their genomes were not accessible to RNase. HBGAs were found to offer GII.4 VLPs no protection against an acid pH or proteolytic enzymes.

Highlights

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide
Histo-Blood Groups Antigens (HBGAs) have been described to be involved in HuNoV infection[15,38,39]
While HBGAs were recently shown to be critical for infection of some HuNoV strains in the human intestinal enteroids s ystem[40], there is no evidence that HBGAs are the putative cellular receptor for HuNoVs

Summary

Introduction

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Histo-Blood Groups Antigens (HBGAs) have been described as attachment factors, promoting HuNoV infection. Their role has not yet been elucidated. The effects of acid pH and proteolytic enzymes (pepsin, trypsin, and chymotrypsin) on GII.[4] virus-like particles (VLPs) and GII.[4] HuNoVs were studied, both during interactions and non-interaction with HBGAs. The results showed that GII.[4] VLPs and GII.[4] HuNoVs behaved differently following the treatments. The biosynthesis of HBGAs is governed by the ABO and FUT2 and FUT3 fucosyl-transferase gene families[17,18] They can be found on red blood cells and mucosal epithelial cells. Interactions between HuNoVs and HBGAs are highly specific, with multiple

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