The Viral σ1 Protein and Glycoconjugates Containing α2-3-Linked Sialic Acid Are Involved in Type 1 Reovirus Adherence to M Cell Apical Surfaces

Abstract

Reovirus is a nonenveloped, 85-nm icosahedral pathogen that enters the mouse intestinal Peyer's patch mucosa by adhering to M cells and then exploiting the antigen-transporting activity of these specialized epithelial cells (2,50,73). When introduced into the intestinal lumens of adult mice, reovirus type 1 Lang (T1L) adheres to the apical surfaces of M cells but generally not to those of enterocytes, which cover the vast majority of the mucosa. It is known that T1L infection of the mouse mucosa in vivo requires proteolytic processing of the viral outer capsid by enzymes in the intestinal lumen (6, 9, 45). The resulting infectious subviral particles (ISVPs) have a cleaved form of the membrane penetration protein 1, have lost the 1-protecting protein 3, and may have the viral hemagglutinin 1 in a more extended conformation than that found in virions (18,20,38,44,45,48). We have previously shown that conversion of T1L virions to ISVPs is required for adherence to M cells in adult mice (2), but neither the T1L protein that mediates binding nor the M cell component recognized by that protein has been identified.The 1 protein serves as the viral adhesin that mediates hemagglutination (HA) and binding to several different types of cultured cells (3,

Genetic Determinants of Reovirus Pathogenesis in a Murine Model of Respiratory Infection

“…The T3D C change at nucleotide 77 confers a valine-to-alanine change at position 22 in the 1 tail and a glutamine-to-histidine change at position 3 in 1s, whereas nucleotide 1234 confers a threonine-to-alanine change at position 408 in the 1 head. These residues are not associated with any known antibody epitope, receptor-binding site, or protease-sensitive region (7,8,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). Interestingly, our F virions were treated with HAT protease for 2 h at the concentrations shown.…”

Transient infection of freshly isolated human colorectal tumor cells by reovirus T3D intermediate subviral particles

“…Many colorectal tumors retain the capacity to form a mucus layer 22,23 and this may interfere with the infection of tumor cells by oncolytic viruses like reovirus T3D. 24 Interestingly, s1 from reovirus T3D possesses a latent glycosyl hydrolase activity that is uncovered during the generation of ISVPs. It has been suggested that ISVPs utilize this activity to hydrolyze (part of) the glycosidic portion of the mucus layer to allow infection of otherwise resistant cells.…”

“…After washing, the membrane was incubated for 1 h with swine anti-rabbit-RPO (Dako) (1:5000). The signals were visualized using an enhanced chemiluminescence system (Roche) 24 h after labeling and cell extracts or tumor fragments were prepared in sample buffer and were analyzed with electrophoresis on long 45 cm sodium dodecyl sulfatepolyacrylamide gel. Gels were dried and exposed to radiographic film.…”

Manning the Barricades: Role of the Gut Epithelium in Crohn’s Disease

“…Such pathogens include EHEC and EPEC strains of Escherichia coli (Fitzhenry et al, 2002;Phillips et al, 2000), as well as Shigella flexneri and Salmonella typhymurium (Jensen et al, 1998). Viruses may also use M cells as a point of entry and specific receptors for HIV (Fotopoulos et al, 2002) and reovirus (Helander et al, 2003) on M cells have been identified.…”