Sample sizes in control groups, PID3 groups, PID3 colonized pigs, and virus titer on PID3 was significantly lower in colonized pigs (Fig. of enterocytes was confirmed, however contamination of B cells was not observed in ileum, and the entire lamina propria in sections of duodenum, jejunum, and ileum were HuNoV-negative. In summary, inhibited HuNoV infectivity, and B cells were not a target cell type for HuNoV in gnotobiotic pigs, with or without colonization. Human noroviruses (HuNoVs), non-enveloped positive-strand RNA viruses, are the leading cause of viral epidemic acute gastroenteritis worldwide1. HuNoVs infect people of all ages, U18666A the gastroenteritis is usually characteristically self-limiting with a duration of 1 1 to 3 days, but it can be severe and prolonged in infants, young children, elderly, and immunocompromised individuals2. As members of the genus in the family, noroviruses are divided into six genogroups (GI – GVI) based on viral capsid gene sequences, but only GI, GII, and GIV are found in humans and thus known as HuNoVs3. Although at least 32 different HuNoV genotypes have been further classified4, genogroup II genotype 4 (GII.4) has been the predominant genotype causing global acute gastroenteritis outbreaks5. In the past two decades, six major epidemics have occurred due to novel GII.4 variants that evolved by recombination and mutation, including the most recent strain, GII.4 Sydney_20126. MHS3 During the season of 2014C2015, newly emerging GII.17 variants caused outbreaks in Asia, and the urgent need to control the global spread of GII.17 has gained recent attention7,8,9. Unfortunately, no vaccines or virus-specific therapies are currently available to prevent or treat HuNoV contamination10. HuNoV research has long been impeded by the lack of a robust cultivation system and a suitable animal model. Limited knowledge of HuNoV biology are mainly from viral contamination studies in chimpanzees11, gnotobiotic (Gn) calves and pigs12,13,14,15, immunodeficient mice16, and human volunteers2. was screened from commensal enteric bacteria with surface histo-blood group antigen (HBGA) expression and the ability to bind to HuNoV specifically17. was subsequently found to promote HuNoV contamination of human B cells (BJAB cell line) studies to support the role of or other HBGA-expressing enteric bacteria in enhancing HuNoV contamination U18666A of B cells. In addition, the low-level viral replication in such cultured B cells was inconsistent with high-level virus shedding in human patients, suggesting that B cells might not be the major target cell type of HuNoV20. Therefore, evidence is essential to test the stimulatory role of and to confirm that B cells are a natural target for robust HuNoV contamination and replication. The neonatal Gn pigs recapitulate the hallmark features of the gastrointestinal tract in young children and have been widely used for enteric U18666A virus contamination21,22. HuNoV pathogenesis studies and vaccine evaluations in Gn pigs have high translational relevance to those of humans13,14,23. Compared to chimpanzees (no longer available for biomedical research) and immunodeficient mice, Gn pigs are currently preferable for HuNoV contamination study in many ways, such as the ability to become infected via oral route and resulting in diarrhea and fecal virus shedding24. In addition, the germ-free environment in the Gn system has enabled the studies of conversation between virus and specific bacterial strains25,26,27, as well as human microbiota28,29. In this study, via colonization in the well-established neonatal Gn pig model of HuNoV contamination and diarrhea, we aimed to (i) elucidate the effects of on HuNoV infectivity reduced HuNoV shedding but not diarrhea To evaluate the effects of on HuNoV contamination and diseases on 3, 4, and 5 days of age. Together with another group of control pigs, all were inoculated with 2.74??104 genome copies of HuNoV GII.4/2006b at 6 days of age, which was post inoculation day 0 (PID0), then euthanized on PID3, PID7, or PID10. To confirm the colonization of in these Gn U18666A pigs, fecal shedding was decided daily from PID0 to euthanasia day. was detected in all treated pigs (Fig. 1), whereas the control pigs remained sterile throughout this study (data not shown). Open in a separate window Physique 1 Fecal shedding.Colonization of in the Gn pigs.
