Abstract
Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney), and GI.3, and IFN-γ production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539-amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-γ in response to the peptides and five subjects produced IFN-γ in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151) was identified in two subjects, both having human leukocyte antigen (HLA)-A∗02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.
Highlights
Norovirus (NoV) is recognized as a leading cause of acute gastroenteritis in children and adults worldwide (Hall et al, 2016)
Following NoV infection/challenge, interferon gamma (IFN-γ) secretion by CD4+ T cells has been analyzed only by enzyme-linked immunosorbent assay (ELISA) using NoV virus-like particle (VLP) as antigens, and the results indicated the generation of NoV-specific memory T cell responses (Lindesmith et al, 2005, 2010)
VLPs were used as antigens in an ELISA to test plasma immunoglobulin G (IgG) antibody binding to native, conformational antigenic determinants
Summary
Norovirus (NoV) is recognized as a leading cause of acute gastroenteritis in children and adults worldwide (Hall et al, 2016). According to a recently published WHO report, NoVs caused 120 million cases of diarrheal diseases, more than any other foodborne or infectious agent (Havelaar et al, 2015). These non-enveloped RNA viruses belonging to Caliciviridae family are highly infectious and cause frequent outbreaks that can be serious to individuals with underlying conditions, the elderly, and young children (Hall et al, 2016). There is no cure or preventive vaccine available against NoV gastroenteritis
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