Rotavirus Interactions With Host Intestinal Epithelial Cells

Abstract

Rotavirus (RV) is the foremost enteric pathogen associated with severe diarrheal illness in young children (<5years) and animals worldwide. RV primarily infects mature enterocytes in the intestinal epithelium causing villus atrophy, enhanced epithelial cell turnover and apoptosis. Intestinal epithelial cells (IECs) being the first physical barrier against RV infection employs a range of innate immune strategies to counteract RVs invasion, including mucus production, toll-like receptor signaling and cytokine/chemokine production. Conversely, RVs have evolved numerous mechanisms to escape/subvert host immunity, seizing translation machinery of the host for effective replication and transmission. RV cell entry process involve penetration through the outer mucus layer, interaction with cell surface molecules and intestinal microbiota before reaching the IECs. For successful cell attachment and entry, RVs use sialic acid, histo-blood group antigens, heat shock cognate protein 70 and cell-surface integrins as attachment factors and/or (co)-receptors. In this review, a comprehensive summary of the existing knowledge of mechanisms underlying RV-IECs interactions, including the role of gut microbiota, during RV infection is presented. Understanding these mechanisms is imperative for developing efficacious strategies to control RV infections, including development of antiviral therapies and vaccines that target specific immune system antagonists within IECs.

Engineering a Vaccine Platform using Rotavirus A to Express SARS-CoV-2 Spike Epitopes

“…At 24 hpi, VP6 was predominantly detected in the epithelium comprised of mature enterocytes lining the apical surface of the organoid lumen (Fig. 7A), which is consistent with previous findings showing their preferential infection by RVs [19, 20]. In contrast, VP6 distribution in RBM and T2A_RBM mutants was detected around the nuclei of cells located within the organoid lumen and in the punctate cytoplasmic inclusion bodies, most likely viroplasms, sites of RV replication and assembly [1] (Fig.…”

“…A double-layered particle (DLP), nested within the TLP, contains the intermediate and inner layers of the capsid [1]. RV primarily infects mature enterocytes of the intestinal epithelium and replicates exclusively in the cytoplasm [19,20].…”

“…Efficient RV cell entry requires proteolytic cleavage of the outer capsid protein, VP4, into VP8* (28kDa) and VP5* (60kDa) domains by trypsin-like proteases of the host gastrointestinal tract [21][22][23]. The VP8* lectin domain mediates RV attachment to different host cell receptors such as sialic acid-containing glycans, histo-blood group antigens and integrins, depending on the virus strain [20,[24][25][26]. Low calcium levels trigger dissociation of VP7 and VP4, releasing the transcriptionally active DLP into the cytoplasm [1].…”

“…A double-layered particle (DLP), nested within the TLP, contains the intermediate and inner layers of the capsid [1]. RV primarily infects mature enterocytes of the intestinal epithelium and replicates exclusively in the cytoplasm [19, 20]. Efficient RV cell entry requires proteolytic cleavage of the outer capsid protein, VP4, into VP8* (28kDa) and VP5* (60kDa) domains by trypsin-like proteases of the host gastrointestinal tract [21–23].…”

Identification of Pulmonary Infections With Porcine Rotavirus A in Pigs With Respiratory Disease

“…While 10 groups of RVs have been described, group A RVs (RVA) are the best studied as they are found in a wide array of species including pigs, humans, cattle, and poultry (4). It is well known that RVs infect mature enterocytes in the small intestine leading to disruption of the intestinal mucosal barrier and the development of diarrhea (2,5). While RV principally replicates in intestinal epithelial cells, several studies have detected RV in serum and multiple visceral organs, suggesting viremia (5)(6)(7)(8)(9)(10)(11).…”