1887

Abstract

The role of commensal microbiota in enteric viral infections has been explored extensively, but the interaction between human gut microbiota (HGM) and human norovirus (HuNoV) is poorly understood. In this study, we established an HGM-Transplanted gnotobiotic (Gn) pig model of HuNoV infection and disease, using an infant stool as HGM transplant and a HuNoV GII.4/2006b strain for virus inoculation. Compared to germ-free Gn pigs, HuNoV inoculation in HGMT Gn pigs resulted in increased HuNoV shedding, characterized by significantly higher shedding titres on post inoculation day (PID) 3, 4, 6, 8 and 9, and significantly longer mean duration of virus shedding. In addition, virus titres were significantly higher in duodenum and distal ileum of HGMT Gn pigs on PID10, while comparable and transient HuNoV viremia was detected in both groups. 16S rRNA gene sequencing demonstrated that HuNoV infection dramatically altered intestinal microbiota in HGMT Gn pigs at the phylum (Proteobacteria, Firmicutes and Bacteroidetes) and genus (, , , , , and ) levels. In summary, enhanced GII.4 HuNoV infection was observed in the presence of HGM, and host microbiota was susceptible to disruption upon HuNoV infection.

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2019-11-01
2024-11-12
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References

  1. Atmar RL, Ramani S, Estes MK. Human noroviruses: recent advances in a 50-year history. Curr Opin Infect Dis 2018; 31:422–432 [View Article]
    [Google Scholar]
  2. Hall AJ, Glass RI. Parashar UD: new insights into the global burden of noroviruses and opportunities for prevention. Expert Rev Vaccines 20161–3
    [Google Scholar]
  3. Bartsch SM, Lopman BA, Ozawa S, Hall AJ, Lee BY. Global economic burden of norovirus gastroenteritis. PLoS One 2016; 11:e0151219 [View Article]
    [Google Scholar]
  4. Riddle MS, Walker RI. Status of vaccine research and development for norovirus. Vaccine 2016; 34:2895–2899 [View Article]
    [Google Scholar]
  5. Kuss SK, Best GT, Etheredge CA, Pruijssers AJ, Frierson JM et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 2011; 334:249–252 [View Article]
    [Google Scholar]
  6. Kane M, Case LK, Kopaskie K, Kozlova A, MacDearmid C et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 2011; 334:245–249 [View Article]
    [Google Scholar]
  7. Uchiyama R, Chassaing B, Zhang B, Gewirtz AT. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J Infect Dis 2014; 210:171–182 [View Article]
    [Google Scholar]
  8. Jones MK, Watanabe M, Zhu S, Graves CL, Keyes LR et al. Enteric bacteria promote human and mouse norovirus infection of B cells. Science 2014; 346:755–759 [View Article]
    [Google Scholar]
  9. Baldridge MT, Nice TJ, McCune BT, Yokoyama CC, Kambal A et al. Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection. Science 2015; 347:266–269 [View Article]
    [Google Scholar]
  10. Ivanov II, Honda K. Intestinal commensal microbes as immune modulators. Cell Host Microbe 2012; 12:496–508 [View Article]
    [Google Scholar]
  11. Thackray LB, Handley SA, Gorman MJ, Poddar S, Bagadia P et al. Oral antibiotic treatment of mice exacerbates the disease severity of multiple flavivirus infections. Cell Rep 2018; 22:e34463440–3453 [View Article]
    [Google Scholar]
  12. Walker FC, Baldridge MT. Interactions between noroviruses, the host, and the microbiota. Curr Opin Virol 2019; 37:1–9 [View Article]
    [Google Scholar]
  13. Nelson AM, Walk ST, Taube S, Taniuchi M, Houpt ER et al. Disruption of the human gut microbiota following norovirus infection. PLoS One 2012; 7:e48224 [View Article]
    [Google Scholar]
  14. Rodríguez-Díaz J, García-Mantrana I, Vila-Vicent S, Gozalbo-Rovira R, Buesa J et al. Relevance of secretor status genotype and microbiota composition in susceptibility to rotavirus and norovirus infections in humans. Sci Rep 2017; 7:45559 [View Article]
    [Google Scholar]
  15. Kolawole AO, Rocha-Pereira J, Elftman MD, Neyts J, Wobus CE. Inhibition of human norovirus by a viral polymerase inhibitor in the B cell culture system and in the mouse model. Antiviral Res 2016; 132:46–49 [View Article]
    [Google Scholar]
  16. Lei S, Samuel H, Twitchell E, Bui T, Ramesh A et al. Enterobacter cloacae inhibits human norovirus infectivity in gnotobiotic pigs. Sci Rep 2016; 6:25017 [View Article]
    [Google Scholar]
  17. Ettayebi K, Crawford SE, Murakami K, Broughman JR, Karandikar U et al. Replication of human noroviruses in stem cell-derived human enteroids. Science 2016; 353:1387–1393 [View Article]
    [Google Scholar]
  18. Costantini V, Morantz EK, Browne H, Ettayebi K, Zeng X-L et al. Human norovirus replication in human intestinal enteroids as model to evaluate virus inactivation. Emerg Infect Dis 2018; 24:14531464 [View Article]
    [Google Scholar]
  19. Lei S, Twitchell E, Pathogenesis YuanL. Immunity and the role of microbiome/probiotics in enteric virus infections in humans and animal models. In Sun J, Dudeja PK. (editors) Mechanisms Underlying Host-Microbiome Interactions in Pathophysiology of Human Diseases Boston, MA: Springer US; 2018 pp 55–78
    [Google Scholar]
  20. Kocher J, Bui T, Giri-Rachman E, Wen K, Li G et al. Intranasal P particle vaccine provided partial cross-variant protection against human GII.4 norovirus diarrhea in gnotobiotic pigs. J Virol 2014; 88:9728–9743 [View Article]
    [Google Scholar]
  21. Bui T, Li G, Kim I, Wen K, Twitchell EL et al. Effects of racecadotril on weight loss and diarrhea due to human rotavirus in neonatal gnotobiotic pigs (sus scrofa domesticus). Comp Med 2017; 67:157–164
    [Google Scholar]
  22. Yang X, Twitchell E, Li G, Wen K, Weiss M et al. High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity. Sci Rep 2015; 5:15004 [View Article]
    [Google Scholar]
  23. Wen X, Cao D, Jones RW, Hoshino Y, Yuan L. Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic. Hum Vaccin Immunother 2015; 11:2483–2489 [View Article]
    [Google Scholar]
  24. Lei S, Yuan L. Chapter 21 - Rice Bran Usage in Diarrhea. In Watson RR. editor Dietary Interventions in Gastrointestinal Diseases Preedy VR: Academic Press; 2019 pp 257–263
    [Google Scholar]
  25. Todd K, Tripp R. Human norovirus: experimental models of infection. Viruses 2019; 11:151 [View Article]
    [Google Scholar]
  26. Zhang H, Wang H, Shepherd M, Wen K, Li G et al. Probiotics and virulent human rotavirus modulate the transplanted human gut microbiota in gnotobiotic pigs. Gut Pathog 2014; 6:39 [View Article]
    [Google Scholar]
  27. Kumar A, Vlasova AN, Deblais L, Huang HC, Wijeratne A et al. Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model. BMC Gastroenterol 2018; 18:93 [View Article]
    [Google Scholar]
  28. Twitchell EL, Tin C, Wen K, Zhang H, Becker-Dreps S et al. Modeling human enteric dysbiosis and rotavirus immunity in gnotobiotic pigs. Gut Pathog 2016; 8:51 [View Article]
    [Google Scholar]
  29. Miyazaki A, Kandasamy S, Michael H, Langel SN, Paim FC et al. Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model. Vaccine 2018; 36:6270–6281 [View Article]
    [Google Scholar]
  30. De Vadder F, Grasset E, Mannerås Holm L, Karsenty G, Macpherson AJ et al. Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks. Proc Natl Acad Sci USA 2018; 115:6458–6463 [View Article]
    [Google Scholar]
  31. An R, Wilms E, Masclee AAM, Smidt H, Zoetendal EG et al. Age-Dependent changes in Gi physiology and microbiota: time to reconsider?. Gut 2018; 67:22132222 [View Article]
    [Google Scholar]
  32. Yuan L, Jobst PM, Weiss M. Gnotobiotic pigs: from establishing facility to modeling human infectious diseases. In Schoeb TR. editor Gnotobiotics Eaton KA: Academic Press; 2017 pp 349–368
    [Google Scholar]
  33. Robinson CM, Jesudhasan PR, Pfeiffer JK. Bacterial lipopolysaccharide binding enhances virion stability and promotes environmental fitness of an enteric virus. Cell Host Microbe 2014; 15:36–46 [View Article]
    [Google Scholar]
  34. Miura T, Sano D, Suenaga A, Yoshimura T, Fuzawa M et al. Histo-Blood group antigen-like substances of human enteric bacteria as specific adsorbents for human noroviruses. J Virol 2013; 87:9441–9451 [View Article]
    [Google Scholar]
  35. Almand EA, Moore MD, Outlaw J, Jaykus LA. Human norovirus binding to select bacteria representative of the human gut microbiota. PLoS One 2017; 12:e0173124 [View Article]
    [Google Scholar]
  36. Rubio-del-Campo A, Coll-Marqués JM, Yebra MJ, Buesa J, Pérez-Martínez G et al. Noroviral p-particles as an in vitro model to assess the interactions of noroviruses with probiotics. PLoS One 2014; 9:e89586 [View Article]
    [Google Scholar]
  37. Lei S, Ramesh A, Twitchell E, Wen K, Bui T et al. High protective efficacy of probiotics and rice bran against human norovirus infection and diarrhea in gnotobiotic pigs. Front Microbiol 2016; 7:1699 [View Article]
    [Google Scholar]
  38. Li D, Breiman A, le Pendu J, Uyttendaele M. Binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress. Front Microbiol 2015; 6:659 [View Article]
    [Google Scholar]
  39. Jones MK, Grau KR, Costantini V, Kolawole AO, de Graaf M et al. Human norovirus culture in B cells. Nat Protoc 2015; 10:1939–1947 [View Article]
    [Google Scholar]
  40. Agus SG, Dolin R, Wyatt RG, Tousimis AJ, Northrup RS. Acute infectious nonbacterial gastroenteritis: intestinal histopathology. histologic and enzymatic alterations during illness produced by the Norwalk agent in man. Ann Intern Med 1973; 79:18–25 [View Article]
    [Google Scholar]
  41. Dolin R, Levy AG, Wyatt RG, Thornhill TS, Gardner JD. Viral gastroenteritis induced by the Hawaii agent. jejunal histopathology and serologic response. Am J Med 1975; 59:761–768 [View Article]
    [Google Scholar]
  42. Karst SM, Wobus CE, Goodfellow IG, Green KY. Virgin HW: Advances in norovirus biology. Cell Host Microbe 2014; 15:668–680
    [Google Scholar]
  43. Karandikar UC, Crawford SE, Ajami NJ, Murakami K, Kou B et al. Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients. J Gen Virol 2016; 97:2291–2300 [View Article]
    [Google Scholar]
  44. Cheetham S, Souza M, Meulia T, Grimes S, Han MG et al. Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs. J Virol 2006; 80:10372–10381 [View Article]
    [Google Scholar]
  45. Bui T, Kocher J, Li Y, Wen K, Li G et al. Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age. J Gen Virol 2013; 94:2005–2016 [View Article]
    [Google Scholar]
  46. Lei S, Ryu J, Wen K, Twitchell E, Bui T et al. Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency. Sci Rep 2016; 6:25222 [View Article]
    [Google Scholar]
  47. Wilen CB, Lee S, Hsieh LL, Orchard RC, Desai C et al. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 2018; 360:204–208 [View Article]
    [Google Scholar]
  48. Chen SY, Tsai CN, Lee YS, Lin CY, Huang KY et al. Intestinal microbiome in children with severe and complicated acute viral gastroenteritis. Sci Rep 2017; 7:46130 [View Article]
    [Google Scholar]
  49. Ma C, Wu X, Nawaz M, Li J, Yu P et al. Molecular characterization of fecal microbiota in patients with viral diarrhea. Curr Microbiol 2011; 63:259–266 [View Article]
    [Google Scholar]
  50. Stewart CJ, Ajami NJ, O'Brien JL, Hutchinson DS, Smith DP et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 2018; 562:583–588 [View Article]
    [Google Scholar]
  51. Becker-Dreps S, Vilchez S, Bucardo F, Twitchell E, Choi WS et al. The association between fecal biomarkers of environmental enteropathy and rotavirus vaccine response in nicaraguan infants. Pediatr Infect Dis J 2017; 36:412–416 [View Article]
    [Google Scholar]
  52. Becker-Dreps S, Allali I, Monteagudo A, Vilchez S, Hudgens MG et al. Gut microbiome composition in young nicaraguan children during diarrhea episodes and recovery. Am J Trop Med Hyg 2015; 93:1187–1193 [View Article]
    [Google Scholar]
  53. Tin CM, Yuan L, Dexter RJ, Parra GI, Bui T et al. A luciferase immunoprecipitation system (lips) assay for profiling human norovirus antibodies. J Virol Methods 2017; 248:116–129 [View Article]
    [Google Scholar]
  54. Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010; 7:335–336 [View Article]
    [Google Scholar]
  55. Lozupone C, Hamady M, Knight R. UniFrac-an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics 2006; 7:371 [View Article]
    [Google Scholar]
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