Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity
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 enhan...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/7/1406 |
| _version_ | 1797587208025145344 |
|---|---|
| author | Molly Raque Sergei A. Raev Yusheng Guo Maryssa K. Kick Linda J. Saif Anastasia N. Vlasova |
| author_facet | Molly Raque Sergei A. Raev Yusheng Guo Maryssa K. Kick Linda J. Saif Anastasia N. Vlasova |
| author_sort | Molly Raque |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:33:53Z |
| format | Article |
| id | doaj.art-08f97ff97a484b3eb42b4cd3f13faf53 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T00:33:53Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-08f97ff97a484b3eb42b4cd3f13faf532023-11-18T21:43:15ZengMDPI AGViruses1999-49152023-06-01157140610.3390/v15071406Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate ImmunityMolly Raque0Sergei A. Raev1Yusheng Guo2Maryssa K. Kick3Linda J. Saif4Anastasia N. Vlasova5Center 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, USACenter 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, USACenter 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, USACenter 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, USACenter 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, USACenter 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, USAAlthough 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.https://www.mdpi.com/1999-4915/15/7/1406rotavirus Atranscriptome analysisglycosyltransferasesfucosyltransferasessialyltransferasescholesterol metabolism |
| spellingShingle | Molly Raque Sergei A. Raev Yusheng Guo Maryssa K. Kick Linda J. Saif Anastasia N. Vlasova Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity Viruses rotavirus A transcriptome analysis glycosyltransferases fucosyltransferases sialyltransferases cholesterol metabolism |
| title | Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity |
| title_full | Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity |
| title_fullStr | Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity |
| title_full_unstemmed | Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity |
| title_short | Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity |
| title_sort | host cell response to rotavirus infection with emphasis on virus glycan interactions cholesterol metabolism and innate immunity |
| topic | rotavirus A transcriptome analysis glycosyltransferases fucosyltransferases sialyltransferases cholesterol metabolism |
| url | https://www.mdpi.com/1999-4915/15/7/1406 |
| work_keys_str_mv | AT mollyraque hostcellresponsetorotavirusinfectionwithemphasisonvirusglycaninteractionscholesterolmetabolismandinnateimmunity AT sergeiaraev hostcellresponsetorotavirusinfectionwithemphasisonvirusglycaninteractionscholesterolmetabolismandinnateimmunity AT yushengguo hostcellresponsetorotavirusinfectionwithemphasisonvirusglycaninteractionscholesterolmetabolismandinnateimmunity AT maryssakkick hostcellresponsetorotavirusinfectionwithemphasisonvirusglycaninteractionscholesterolmetabolismandinnateimmunity AT lindajsaif hostcellresponsetorotavirusinfectionwithemphasisonvirusglycaninteractionscholesterolmetabolismandinnateimmunity AT anastasianvlasova hostcellresponsetorotavirusinfectionwithemphasisonvirusglycaninteractionscholesterolmetabolismandinnateimmunity |