Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients

Umesh C. Karandikar, Sue E. Crawford, Nadim J. Ajami, Kosuke Murakami, Baijun Kou, Khalil Ettayebi, Genovefa A. Papanicolaou, Ubonvan Jongwutiwes, Miguel Angel Perales, Jinru Shia, David Mercer, Milton J. Finegold, Jan Vinjé, Robert L. Atmar, Mary K. Estes

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Article number000545
Pages (from-to)2291-2300
Number of pages10
JournalJournal of General Virology
Volume97
Issue number9
DOIs
StatePublished - Sep 2016

Keywords

  • Enterocytes
  • Immunocompromised patients
  • Intestinal biopsy
  • Norovirus replication
  • Transplant patients

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Karandikar, U. C., Crawford, S. E., Ajami, N. J., Murakami, K., Kou, B., Ettayebi, K., Papanicolaou, G. A., Jongwutiwes, U., Perales, M. A., Shia, J., Mercer, D., Finegold, M. J., Vinjé, J., Atmar, R. L., & Estes, M. K. (2016). Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients. Journal of General Virology, 97(9), 2291-2300. [000545]. https://doi.org/10.1099/jgv.0.000545