title: Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients.
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.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Umesh C
authors.initials: UC
authors.lastname: Karandikar
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Sue E
authors.initials: SE
authors.lastname: Crawford
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Baijun
authors.initials: B
authors.lastname: Kou
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Khalil
authors.initials: K
authors.lastname: Ettayebi
authors.affiliation: Infectious Disease and Adult Bone Marrow Transplant Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Genovefa A
authors.initials: GA
authors.lastname: Papanicolaou
authors.affiliation: Infectious Disease and Adult Bone Marrow Transplant Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ubonvan
authors.initials: U
authors.lastname: Jongwutiwes
authors.affiliation: Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Cornell Medical College, New York, NY , USA.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.affiliation: Department of Surgery, University for Nebraska Medical Centre, Omaha, NE 68198, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mercer
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vinjé
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
mesh_terms: D000956:Antigens, Viral / Q000032:analysis; D001706:Biopsy; D017250:Caliciviridae Infections / Q000473:pathology / Q000821:virology*; D036022:Capsid Proteins / Q000032:analysis; D002908:Chronic Disease; D006651:Histocytochemistry; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology / Q000821:virology*; D008853:Microscopy; D029322:Norovirus / Q000302:isolation & purification*; D066027:Transplant Recipients
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins