Abstract
Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385–400 and 401–420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.
Highlights
Noroviruses (NoVs) are a group of non-enveloped RNA viruses belonging to the Norovirus genus in the Caliciviridae family, and they are the leading cause of sporadic and epidemic nonbacterial acute gastroenteritis (AGE) in humans [1,2,3]
The 8C7 epitope overlaps with the histo-blood group antigens (HBGA) binding site (HBS), while the 8D1 epitope is spatially adjacent to HBS
Information on blockade antibody epitopes of specific NoV genotypes is important for Information on blockade ofand specific
Summary
Noroviruses (NoVs) are a group of non-enveloped RNA viruses belonging to the Norovirus genus in the Caliciviridae family, and they are the leading cause of sporadic and epidemic nonbacterial acute gastroenteritis (AGE) in humans [1,2,3]. Based on the VP1 amino acid sequence, NoVs were classified into six genogroups (GI to GVI) in 2013 [14]. This NoV classification scheme was recently updated, with the number of genogroups expanded to 10 (GI to GX) [3,14]. Viruses of GI, GII, and GIV infect humans, and in particular, GII, which comprises 27 genotypes [14], accounts for approximately 90% of norovirus infections in humans [15]. One clinical study showed that GII. and GII. were responsible for 71.24% and 23.53% of NoV-associated pediatric
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