Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients

Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine

“…Since persistent viral shedding of MNoV in mice resembles the prolonged viral shedding seen in asymptomatic HNoV-infected patients after resolution of acute infection, the IEC tropism of MNoV may also apply to HNoV. This would be consistent with studies identifying IECs as an important cell type for HNoV replication (Ettayebi et al, 2016; Karandikar et al, 2016). Bile acids have been identified as an important factor for HNoV cultivation in enterocytes (Ettayebi et al, 2016), which may correlate with a requirement for intestinal microbes for infection by MNoV strain CR6 (Baldridge et al, 2015); the exploration of the role of host and microbial metabolites in IEC infection will be important for future study.…”

“…HNoV cellular tropism in the intestine has not yet been elucidated in an immunocompetent host in vivo , which has been a barrier to understanding the pathogenesis of HNoV infection. Previous evidence for HNoV cellular tropism has come from immunodeficient human patients (Karandikar et al, 2016), non-human primates (Bok et al, 2011), gnotobiotic pigs (Cheetham et al, 2006), and immunodeficient animals (Taube et al, 2013). Cumulatively these data have suggested that macrophages, dendritic cells, B-cells and IECs are all potential target cells for HNoV (Karst and Wobus, 2015).…”

“…Multiple studies have provided experimental evidence for the cellular tropism of HNoV and MNoV, but the cell type responsible for viral transmission and disease symptoms has not yet been elucidated. Exploration of HNoV tropism has mostly relied on immunodeficient human patients (Karandikar et al, 2016) and non-native animal models. HNoV infection in immunocompromised mice showed macrophage-like cell tropism in the liver and spleen (Taube et al, 2013).…”

Norovirus Regulation by Host and Microbe

“…B cells are also targets for HNoVs [4], but other targets exist, since humans deficient in B cells are still susceptible to HNoV infection [39]. Recent immunofluorescence analysis of small intestinal biopsy samples from HNoV-infected immunocompromised patients revealed the presence of HNoV infection in intestinal epithelial cells, CD68 + or DC-SIGN + phagocytes (e.g., macrophages, DCs), and CD3 + cells (T cells or intraepithelial lymphocytes) [40]. A tropism of HNoV for enterocytes was subsequently confirmed by cultivating HNoV in human intestinal enteroid monolayer cultures [5].…”

The Dual Tropism of Noroviruses

“…Evidence for infection of the following cell types in animal models has been obtained: dendritic cells and B cells in chimpanzees (11), macrophages in immunocompromised mice (9), enterocytes in gnotobiotic pigs (13), and macrophages, dendritic cells, and lymphocytes in miniature piglets (43). More importantly, histologic analysis of HuNoV-infected immunocompromised patients further supports a dual tropism (44). HuNoV antigen is detected in enterocytes near the villus tips, as well as CD3-, CD68-, or DC-SIGN-positive cells, immune cell markers for T cells, macrophages, and dendritic cells.…”