Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity
Molly Raque,
Sergei A. Raev,
Yusheng Guo,
Maryssa K. Kick,
Linda J. Saif,
Anastasia N. Vlasova
Affiliations
Molly Raque
Center for Food Animal Health Research Program, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 43210, USA
Sergei A. Raev
Center for Food Animal Health Research Program, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 43210, USA
Yusheng Guo
Center for Food Animal Health Research Program, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 43210, USA
Maryssa K. Kick
Center for Food Animal Health Research Program, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 43210, USA
Linda J. Saif
Center for Food Animal Health Research Program, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 43210, USA
Anastasia N. Vlasova
Center for Food Animal Health Research Program, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Department of Animal Sciences, College of Food Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 43210, USA
Although rotavirus A (RVA) is the primary cause of acute viral gastroenteritis in children and young animals, mechanisms of its replication and pathogenesis remain poorly understood. We previously demonstrated that the neuraminidase-mediated removal of terminal sialic acids (SAs) significantly enhanced RVA-G9P[13] replication, while inhibiting RVA-G5P[7] replication. In this study, we compared the transcriptome responses of porcine ileal enteroids (PIEs) to G5P[7] vs. G9P[13] infections, with emphasis on the genes associated with immune response, cholesterol metabolism, and host cell attachment. The analysis demonstrated that G9P[13] infection led to a robust modulation of gene expression (4093 significantly modulated genes vs. 488 genes modulated by G5P[7]) and a significant modulation of glycosyltransferase-encoding genes. The two strains differentially affected signaling pathways related to immune response, with G9P[13] mostly upregulating and G5P[7] inhibiting them. Both RVAs modulated the expression of genes encoding for cholesterol transporters. G9P[13], but not G5P[7], significantly affected the ceramide synthesis pathway known to affect both cholesterol and glycan metabolism. Thus, our results highlight the unique mechanisms regulating cellular response to infection caused by emerging/re-emerging and historical RVA strains relevant to RVA-receptor interactions, metabolic pathways, and immune signaling pathways that are critical in the design of effective control strategies.
