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J Gen Virol. 2016 Sep;97(9):2291-300. doi: 10.1099/jgv.0.000545. Epub 2016 Jul 12.

Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients.

Author information

1
1​ Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
2
2​ Infectious Disease and Adult Bone Marrow Transplant Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
3
3​ Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA 4​ Weill Cornell Medical College, New York, NY , USA.
4
5​ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
5
6​ Department of Surgery, University for Nebraska Medical Centre, Omaha, NE 68198, USA.
6
7​ Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA 8​ Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
7
9​ Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
8
1​ Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA 10​ Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

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.

PMID:
27412790
PMCID:
PMC5756488
DOI:
10.1099/jgv.0.000545
[Indexed for MEDLINE]
Free PMC Article

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