Abstract
Human norovirus (HuNoV) is the leading cause of global infectious acute gastroenteritis, causing ~20% of reported diarrheal episodes. Typically, GII.4 strains cause 50–70% of yearly outbreaks, and pandemic waves of disease approximately every 2–7 years due to rapid evolution. Importantly, GII.4 dominance is occasionally challenged by the sudden emergence of other GII strains, most recently by GII.2 strains which peaked in 2016–2017, dramatically increasing from 1% to 20% of total HuNoV outbreaks. To determine if viral capsid evolution may account for the sudden rise in GII.2 outbreaks, Virus Like Particles (VLPs) of two 2016–2017 GII.2 strains were compared by antigenic and histo blood group antigen (HBGA) binding profiles to the prototypic 1976 GII.2 Snow Mountain Virus (SMV) strain. Despite >50 years of GII.2 strain persistence in human populations, limited sequence diversity and antigenic differences were identified between strains. However, capsid microvariation did affect HBGA binding patterns, with contemporary strains demonstrating decreased avidity for type A saliva. Furthermore, bile salts increased GII.2 VLP avidity for HBGAs, but did not alter antigenicity. These data indicate that large changes in antigenicity or receptor binding are unlikely to explain GII.2 emergence, in contrast to the pandemic GII.4 strains, and indicate that host factors such as waning or remodeling of serum or mucosal immunity likely contributed to the surge in GII.2 prevalence.
Highlights
Human norovirus (HuNoV) is the leading cause of infectious acute gastroenteritis (AGE), with~685 million cases globally occurring every year [1]
Virus Like Particles (VLPs) utilized in this study were produced by synthesizing HuNoV ORF2 genes optimized for human expression (Bio Basic Inc., Markham, ON, Canada) with ApaI and AscI restriction sites for direct ligation into the pVR21 VEE replicon vector
To determine if the 2016–2017 GII.2 capsid strains had developed residue changes that led to antigenic differences, or an expansion of histo blood group antigen (HBGA) binding profiles significant enough to explain the spike in GII.2 outbreaks during the 2016–2017 norovirus season, we first aligned 23 2016–2017 GII.2 capsid sequences collected globally and compared them to the prototype GII.2 strain, GII.2 1976
Summary
~685 million cases globally occurring every year [1]. Of all reported diarrheal episodes, 20% are HuNoV related, primarily afflicting the young, elderly, and immunocompromised, with over 200,000 deaths per year largely resulting from complications from dehydration and malnutrition [2,3,4,5]. Extensive disease burden within these highly susceptible populations warrants development for an effective HuNoV vaccine, which is complicated by extensive antigenic diversity between HuNoV strains. 50–70% of yearly HuNoV outbreaks are caused by genotype GII. strains, which cause pandemic levels of disease approximately every 2–7 years due to rapid evolution and recombination [1,6,7]. During the 2014–2015 HuNoV winter season, global outbreaks of GII. dramatically increased. During the 2016–2017 HuNoV winter season, global outbreaks of GII. strains dramatically increased, from ~1% to 20% of total HuNoV
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
