Chronic norovirus infection in primary immune deficiency disorders: an international case series

Abstract

While Norovirus (NoV) is thought to replicate in B cells, in this PIDD cohort of CNI, B-cell lymphopenia was common, indicating that the presence of B lymphocytes is not essential for CNI.

A comprehensive characterization of chronic norovirus infection in immunodeficient hosts

“…High numbers of CD21 − CXCR5 − B cells and PD-1 + T cells both imply immunologic “exhaustion.” Diagnosis might be heralded by decreasing lymphocyte counts, which are often driven by iatrogenic immunosuppression (which can also precipitate relapse). The gut mucosa exhibits intraepithelial cytotoxic T-cell lymphocytosis and, with thorough assessment, invariably demonstrates villous atrophy (unlike recent reports 9 ); malabsorption is universal. Cross-transmission within immunodeficiency services appears rare, but we nevertheless advocate strict infection control.…”

Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies

“…Up to 10% of CVID patients develop an inflammatory bowel disease-like disorder, and viral infections are thought to play a key role in its pathogenesis (97). CMV has been implicated (97) but most commonly chronic norovirus infection is cited (78)(79)(80)(81)(82). Interestingly, these patients tend to have very low or absent peripheral B cells (78) and very few plasma cells in their intestine (161).…”

“…CMV has been implicated (97) but most commonly chronic norovirus infection is cited (78)(79)(80)(81)(82). Interestingly, these patients tend to have very low or absent peripheral B cells (78) and very few plasma cells in their intestine (161). Of note, even non-CVID patients that suffer from chronic norovirus infection tend to have absent B cells, suggesting a vital role for these cells against this virus (78).…”

Norovirus Protease Structure and Antivirals Development

“…The primary site of infection for HuNoV is the enterocyte from the small intestine (duodenum, jejunum, and ileum) [112]. Given the evidence that HuNoV can replicate in B cell-deficient patients [113,114], and that the noroviral antigen is not detected in B cells in the lamina propria [112], testing of the inhibitors in HIEs, which more closely resembles the HuNoV infection site, is likely more physiologically suitable. The replication cycle and pathogenesis of HuNoV have been studied in many large-animal models, including pig, calves, rhesus macaque, and chimpanzees [115].…”