Functional and structural characterization of Norovirus GII.6 in recognizing histo-blood group antigens.

Noroviruses (NoVs) are the primary cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs. GII.6 NoV is one of the predominant genotypes in humans, which recognizes the type ABO secretor of HBGAs. However, the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive. In this study, we investigated the binding features of the GII.6 strain to HBGAs using saliva- and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide. We showed that the GII.6 â€‹P domain recognized some A and O secretor's saliva samples, most B secretor's saliva samples, and H disaccharide antigen, but did not bind non-secretors' saliva. Further, we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7 â€‹Å, revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs. Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs, demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity. Finally, structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup. Taken together, our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs, and shed light on NoV evolution, epidemiology, and anti-viral drug development.

Mechanical intestinal obstruction due to isolated diffuse venous malformations in the gastrointestinal tract: A case report and review of literature.

BACKGROUND: Isolated gastrointestinal venous malformations (GIVMs) are extremely rare congenital developmental abnormalities of the venous vasculature. Because of their asymptomatic nature, the diagnosis is often quite challenging. However, as symptomatic GIVMs have nonspecific clinical manifestations, misdiagnosis is very common. Here, we report a case of isolated diffuse GIVMs inducing mechanical intestinal obstruction. A literature review was also conducted to summarize clinical features, diagnostic points, treatment selections and differential diagnosis in order that doctors may have a comprehensive understanding of this disease. CASE SUMMARY: A 50-year-old man presented with recurrent painless gastrointestinal bleeding for two months and failure to pass flatus and defecate with nausea and vomiting for ten days. Digital rectal examination found bright red blood and soft nodular masses 3 cm above the anal verge. Computed tomography showed that part of the descending colon and rectosigmoid colon was thickened with phleboliths in the intestinal wall. Colonoscopy exhibited bluish and reddish multinodular submucosal masses and flat submucosal serpentine vessels. Endoscopic ultrasonography showed anechoic cystic spaces within intestinal wall. The lesions were initially thought to be isolated VMs involving part of the descending colon and rectosigmoid colon. Laparoscopic subtotal proctocolectomy, pull-through transection and coloanal anastomosis and ileostomy were performed. Histopathology revealed intact mucosa and dilated, thin-walled blood vessels in the submucosa, muscularis, and serosa involving the entire colorectum. The patient recovered with complete symptomatic relief during the 52-mo follow-up period. CONCLUSION: The diagnosis of isolated GIVMs is challenging. The information presented here is significant for the diagnosis and management of symptoms.

GII.13/21 Noroviruses Recognize Glycans with a Terminal ß-Galactose via an Unconventional Glycan Binding Site.

Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as host susceptibility factors. GII.13 and GII.21 huNoVs form a unique genetic lineage that emerged from mainstream GII NoVs via development of a new, nonconventional glycan binding site (GBS) that binds Lea antigen. This previous finding raised the question of whether the new GII.13/21 GBS really has such a narrow glycan binding spectrum. In this study, we provide solid phenotypic and structural evidence indicating that this new GBS recognizes a group of glycans with a common terminal ß-galactose (ß-Gal). First, we found that P domain proteins of GII.13/21 huNoVs circulating at different times bound three glycans sharing a common terminal ß-Gal, including Lec, lactose, and mucin core 2. Second, we solved the crystal structures of the GII.13 P dimers in complex with Lec and mucin core 2, which showed that ß-Gal is the major binding saccharide. Third, nonfat milk and lactose blocked the GII.13/21 P domain-glycan binding, which may explain the low prevalence of GII.13/21 viruses. Our data provide new insight into the host interactions and epidemiology of huNoVs, which would help in the control and prevention of NoV-associated diseases.IMPORTANCE Evidence from both phenotypic binding assay and structural study support the observed interactions of human noroviruses (huNoVs) with histo-blood group antigens (HBGAs) as receptors or attachment factors, affecting their host susceptibility. GII.13 and GII.21 genotypes form a unique genetic lineage that differs from the mainstream GII huNoVs in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Lea antigen, we found in this study that they can interact with a group of glycans with a common terminal ß-Gal, including Lec, lactose, and mucin core 2. However, this wide glycan binding spectrum in a unique binding mode of the GII.13/21 huNoVs appears not to increase their prevalence, probably due to the existence of decoy glycan receptors in human gastrointestinal tract limiting their infection. Our findings shed light on the host interaction and epidemiology of huNoVs, which would impact the strategy of huNoV control and prevention.