1887

Abstract

Human noroviruses (HuNoVs) can often cause chronic infections in solid organ and haematopoietic stem cell transplant (HSCT) patients. Based on histopathological changes observed during HuNoV infections, the intestine is the presumed site of virus replication in patients; however, the cell types infected by HuNoVs remain unknown. The objective of this study was to characterize histopathological changes during HuNoV infection and to determine the cell types that may be permissive for HuNoV replication in transplant patients. We analysed biopsies from HuNoV-infected and non-infected (control) transplant patients to assess histopathological changes in conjunction with detection of HuNoV antigens to identify the infected cell types. HuNoV infection in immunocompromised patients was associated with histopathological changes such as disorganization and flattening of the intestinal epithelium. The HuNoV major capsid protein, VP1, was detected in all segments of the small intestine, in areas of biopsies that showed histopathological changes. Specifically, VP1 was detected in enterocytes, macrophages, T cells and dendritic cells. HuNoV replication was investigated by detecting the non-structural proteins, RdRp and VPg. We detected RdRp and VPg along with VP1 in duodenal and jejunal enterocytes. These results provide critical insights into histological changes due to HuNoV infection in immunocompromised patients and propose human enterocytes as a physiologically relevant cell type for HuNoV cultivation.

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2016-09-01
2024-03-28
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References

  1. Agus S. G., Dolin R., Wyatt R. G., Tousimis A. J., Northrup R. S. 1973; Acute infectious nonbacterial gastroenteritis: intestinal histopathology. Histologic and enzymatic alterations during illness produced by the Norwalk agent in man. Ann Intern Med 79:18–25 [View Article][PubMed]
    [Google Scholar]
  2. Alkhouri N., Danziger-Isakov L. 2011; Norovirus and severe chronic gastroenteritis in pediatric stem cell transplantation: the plot thickens. Pediatr Transplant 15:671–672 [View Article][PubMed]
    [Google Scholar]
  3. Bimczok D., Smythies L. E., Waites K. B., Grams J. M., Stahl R. D., Mannon P. J., Peter S., Wilcox C. M., Harris P. R. et al. 2013; Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells. J Immunol 190:6626–6634 [View Article][PubMed]
    [Google Scholar]
  4. Brown J. R., Gilmour K., Breuer J. 2016; Norovirus infections occur in B cell deficient patients. Clin Infect Dis 62:1136–1138 [CrossRef]
    [Google Scholar]
  5. Burns J. W., Greenberg H. B., Shaw R. D., Estes M. K. 1988; Functional and topographical analyses of epitopes on the hemagglutinin (VP4) of the simian rotavirus SA11. J Virol 62:2164–2172
    [Google Scholar]
  6. Crawford S. E., Patel D. G., Cheng E., Berkova Z., Hyser J. M., Ciarlet M., Finegold M. J., Conner M. E., Estes M. K. 2006; Rotavirus viremia and extraintestinal viral infection in the neonatal rat model. J Virol 80:4820–4832 [View Article]
    [Google Scholar]
  7. Criglar J. M., Hu L., Crawford S. E., Hyser J. M., Broughman J. R., Prasad B. V., Estes M. K. 2014; A novel form of rotavirus NSP2 and phosphorylation-dependent NSP2-NSP5 interactions are associated with viroplasm assembly. J Virol 88:786–798 [View Article][PubMed]
    [Google Scholar]
  8. Dolin R., Levy A. G., Wyatt R. G., Thornhill T. S., Gardner J. D. 1975; Viral gastroenteritis induced by the Hawaii agent. Jejunal histopathology and serologic response. Am J Med 59:761–768 [View Article][PubMed]
    [Google Scholar]
  9. Doshi M., Woodwell S., Kelleher K., Mangan K., Axelrod P. 2013; An outbreak of norovirus infection in a bone marrow transplant unit. Am J Infect Control 41:820–823 [View Article][PubMed]
    [Google Scholar]
  10. Duizer E., Schwab K. J., Neill F. H., Atmar R. L., Koopmans M. P., Estes M. K. 2004; Laboratory efforts to cultivate noroviruses. J Gen Virol 85:79–87 [View Article][PubMed]
    [Google Scholar]
  11. Ettayebi K., Crawford S. E., Murakami K., Broughman J. R., Karandikar U., Tenge V. R., Neill F. H., Blutt S. E., Zeng X. L. et al. 2016; Replication of human noroviruses in stem cell-derived human enteroids. Science [Epub ahead of print] PMID:27562956 DOI:10.1126/science.aaf5211 [View Article][PubMed]
    [Google Scholar]
  12. Glass R. I., Parashar U. D., Estes M. K. 2009; Norovirus gastroenteritis. N Engl J Med 361:1776–1785 [View Article][PubMed]
    [Google Scholar]
  13. Green K. Y. 2013; Caliciviridae: the noroviruses. In Fields Virology, 6th edn. pp. 582–608 Edited by Knipe H. P., Howley P. M. Philadelphia: Wolters Kluwer;
    [Google Scholar]
  14. Green K. Y. 2014; Norovirus infection in immunocompromised hosts. Clin Microbiol Infect 20:717–723 [View Article][PubMed]
    [Google Scholar]
  15. Hall A. J. 2012; Noroviruses: the perfect human pathogens?. J Infect Dis 205:1622–1624 [View Article][PubMed]
    [Google Scholar]
  16. Hall A. J., Lopman B. A., Payne D. C., Patel M. M., Gastañaduy P. A., Vinjé J., Parashar U. D. 2013; Norovirus disease in the United States. Emerg Infect Dis 19:1198–1205 [View Article][PubMed]
    [Google Scholar]
  17. Harris J. P., Edmunds W. J., Pebody R., Brown D. W., Lopman B. A. 2008; Deaths from norovirus among the elderly, England and Wales. Emerg Infect Dis 14:1546–1552 [View Article][PubMed]
    [Google Scholar]
  18. Jones M. K., Watanabe M., Zhu S., Graves C. L., Keyes L. R., Grau K. R., Gonzalez-Hernandez M. B., Iovine N. M., Wobus C. E. et al. 2014; Enteric bacteria promote human and mouse norovirus infection of B cells. Science 346:755–759 [View Article]
    [Google Scholar]
  19. Katayama K., Murakami K., Sharp T. M., Guix S., Oka T., Takai-Todaka R., Nakanishi A., Crawford S. E., Atmar R. L., Estes M. K. 2014; Plasmid-based human norovirus reverse genetics system produces reporter-tagged progeny virus containing infectious genomic RNA. Proc Natl Acad Sci U S A 111:E40434052 [View Article][PubMed]
    [Google Scholar]
  20. Kitamoto N., Tanaka T., Natori K., Takeda N., Nakata S., Jiang X., Estes M. K. 2002; Cross-reactivity among several recombinant calicivirus virus-like particles (VLPs) with monoclonal antibodies obtained from mice immunized orally with one type of VLP. J Clin Microbiol 40:2459–2465 [View Article][PubMed]
    [Google Scholar]
  21. Koo H. L., Neill F. H., Estes M. K., Munoz F. M., Cameron A., DuPont H. L., Atmar R. L. 2013; Noroviruses: the most common pediatric viral enteric pathogen at a large university hospital after introduction of rotavirus vaccination. J Pediatric Infect Dis Soc 2:57–60 [View Article][PubMed]
    [Google Scholar]
  22. Lay M. K., Atmar R. L., Guix S., Bharadwaj U., He H., Neill F. H., Sastry K. J., Yao Q., Estes M. K. 2010; Norwalk virus does not replicate in human macrophages or dendritic cells derived from the peripheral blood of susceptible humans. Virology 406:1–11 [View Article]
    [Google Scholar]
  23. Papafragkou E., Hewitt J., Park G. W., Greening G., Vinjé J. 2014; Challenges of culturing human norovirus in three-dimensional organoid intestinal cell culture models. PLoS One 8:e63485 [View Article][PubMed]
    [Google Scholar]
  24. Payne D. C., Vinjé J., Szilagyi P. G., Edwards K. M., Staat M. A., Weinberg G. A., Hall C. B., Chappell J., Bernstein D. I. et al. 2013; Norovirus and medically attended gastroenteritis in US children. N Engl J Med 368:1121–1130 [View Article][PubMed]
    [Google Scholar]
  25. Ramani S., Atmar R. L., Estes M. K. 2014; Epidemiology of human noroviruses and updates on vaccine development. Curr Opin Gastroenterol 30:25–33 [View Article][PubMed]
    [Google Scholar]
  26. Robilotti E., Deresinski S., Pinsky B. A. 2015; Norovirus. Clin Microbiol Rev 28:134–164 [View Article][PubMed]
    [Google Scholar]
  27. Rockx B., de Wit M., Vennema H., Vinjé J., de Bruin E., van Duynhoven Y., Koopmans M. 2002; Natural history of human calicivirus infection: a prospective cohort study. Clin Infect Dis 35:246–253 [View Article][PubMed]
    [Google Scholar]
  28. Roddie C., Paul J. P., Benjamin R., Gallimore C. I., Xerry J., Gray J. J., Peggs K. S., Morris E. C., Thomson K. J., Ward K. N. 2009; Allogeneic hematopoietic stem cell transplantation and norovirus gastroenteritis: a previously unrecognized cause of morbidity. Clin Infect Dis 49:1061–1068 [View Article][PubMed]
    [Google Scholar]
  29. Roos-Weil D., Ambert-Balay K., Lanternier F., Mamzer-Bruneel M.-F., Nochy D., Pothier P., Avettand-Fenoel V., Anglicheau D., Snanoudj R. et al. 2011; Impact of norovirus/sapovirus-related diarrhea in renal transplant recipients hospitalized for diarrhea. Transplantation 92:61–69 [View Article]
    [Google Scholar]
  30. Saif M. A., Bonney D. K., Bigger B., Forsythe L., Williams N., Page J., Babiker Z. O., Guiver M., Turner A. J. et al. 2011; Chronic norovirus infection in pediatric hematopoietic stem cell transplant recipients: A cause of prolonged intestinal failure requiring intensive nutritional support. Pediatr Transplant 15:505–509 [View Article][PubMed]
    [Google Scholar]
  31. Schreiber D. S., Blacklow N. R., Trier J. S. 1973; The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis. N Engl J Med 288:1318–1323 [View Article][PubMed]
    [Google Scholar]
  32. Schreiber D. S., Blacklow N. R., Trier J. S. 1974; The small intestinal lesion induced by Hawaii agent acute infectious nonbacterial gastroenteritis. J Infect Dis 129:705–708 [View Article][PubMed]
    [Google Scholar]
  33. Schwartz S., Vergoulidou M., Schreier E., Loddenkemper C., Reinwald M., Schmidt-Hieber M., Flegel W. A., Thiel E., Schneider T. 2011; Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation. Blood 117:5850–5856 [View Article]
    [Google Scholar]
  34. Shi S. R., Chaiwun B., Young L., Cote R. J., Taylor C. R. 1993; Antigen retrieval technique utilizing citrate buffer or urea solution for immunohistochemical demonstration of androgen receptor in formalin-fixed paraffin sections. J Histochem Cytochem 41:1599–1604 [View Article][PubMed]
    [Google Scholar]
  35. Straub T. M., Höner zu Bentrup K., Orosz-Coghlan P., Dohnalkova A., Mayer B. K., Bartholomew R. A., Valdez C. O., Bruckner-Lea C. J., Gerba C. P. et al. 2007; In vitro cell culture infectivity assay for human noroviruses. Emerg Infect Dis 13:396–403 [View Article][PubMed]
    [Google Scholar]
  36. Takanashi S., Saif L. J., Hughes J. H., Meulia T., Jung K., Scheuer K. A., Wang Q. 2014; Failure of propagation of human norovirus in intestinal epithelial cells with microvilli grown in three-dimensional cultures. Arch Virol 159:257–266 [View Article][PubMed]
    [Google Scholar]
  37. Vega E., Barclay L., Gregoricus N., Williams K., Lee D., Vinjé J. 2011; Novel surveillance network for norovirus gastroenteritis outbreaks, United States. Emerg Infect Dis 17:1389–1395
    [Google Scholar]
  38. Vongpunsawad S., Venkataram Prasad B. V., Estes M. K. 2013; Norwalk virus minor capsid protein VP2 associates within the VP1 shell domain. J Virol 87:4818–4825 [View Article][PubMed]
    [Google Scholar]
  39. Woodward J. M., Gkrania-Klotsas E., Cordero-Ng A. Y., Aravinthan A., Bandoh B. N., Liu H., Davies S., Zhang H., Stevenson P. et al. 2015; The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency. Am J Gastroenterol 110:320–327 [View Article][PubMed]
    [Google Scholar]
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