Characterization of a histo-blood group antigen-like substance in romaine lettuce that contributes to human norovirus attachment

Authors: ZHANG, ZILEI - SHANGHAI JIAOTONG UNIVERSITY; LIU, DANLEI - SHANGHAI JIAOTONG UNIVERSITY; WU, QINGPING - GUANGDONG ACADEMY OF AGRICULTURAL SCIENCES; LU, YU - NORTHWEST AGRICULTURAL UNIVERSITY; Tian, Peng; WANG, ZHONGFU - NORTHWEST AGRICULTURE AND FORESTRY UNIVERSITY; WANG, DAPENG - SHANGHAI JIAOTONG UNIVERSITY

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/22/2019
Publication Date: 11/22/2019
Citation: Zhang, Z., Liu, D., Wu, Q., Lu, Y., Tian, P., Wang, Z., Wang, D. 2019. Characterization of a histo-blood group antigen-like substance in romaine lettuce that contributes to human norovirus attachment. Journal of Agricultural and Food Chemistry. 68(5):1207-1212. https://doi.org/10.1021/acs.jafc.9b05887.
DOI: https://doi.org/10.1021/acs.jafc.9b05887

Interpretive Summary: Human noroviruses (HuNoVs) are one of the primary pathogens causing acute nonbacterial gastroenteritis worldwide. Histo-blood group antigens (HBGAs) have been widely accepted as receptors/coreceptors in the recognition and specific binding of HuNoVs. However, it is difficult to separate, enrich and characterize candidate viral ligands from the food matrix and natural sources4. The study of HBGAs and HBGA-like carbohydrates remains a major challenge. Here we show that an oligosaccharide (m/z: 1042, H2N2F2) separated from romaine lettuce extract was involved in specific binding to HuNoVs particles. We found the structure of this oligosaccharide is a chimera of type A and Lewis A HBGA, which also contained the active structure of type H HBGA. The data were consistent with our ELISA results. This structure could be an evidence that the binding of HuNoVs particles with lettuce was specific, and an answer of the HBGA-like carbohydrates previously proposed by investigators. Our results revealed a way to the mechanism of attachment between HuNoVs and lettuce, explained the mode of transmission of HuNoVs with vegetables and provided a theoretical basis for the prevention and control of HuNoVs on produce. We anticipate our assay to be the first answer sheet to the HBGA-like carbohydrates that involved in the specific binding of HuNoVs to lettuce. On this basis, the mechanism of viral transmission with vegetables, fruits and shellfishes could be easily uncovered. Furthermore, this chimera may also provide a novel helper for culture of HuNoVs in vitro.

Technical Abstract: Human noroviruses (HuNoVs) are among the main pathogens causing acute nonbacterial gastroenteritis. Histoblood group antigens (HBGAs) are widely accepted receptors for HuNoV specific binding. HBGA-like substances in produce are also considered as the critical ligands for capture of HuNoVs. However, the composition of viral ligands from food substrates remains unknown. In this study, an oligosaccharide (H2N2F2) was captured and isolated from romaine lettuce extract by a bacterial surface display system. Using electrospray ionization mass spectrometry and tandem mass spectrometry, it was shown that H2N2F2 was most likely to be a chimera of type A, H, and Lewis a HBGAs. The composition was consistent with our ELISA results using a panel of monoclonal antibodies against HBGAs. Our results revealed a possible interaction mechanism between HuNoVs and romaine lettuce. Better understanding of the interaction of HuNoVs with easily contaminated produce will ultimately aid in the control of and reduction in disease outbreaks.