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.
Viruses. 2023 Jun 21;15(7):1406. doi: 10.3390/v15071406.
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.
虽然轮状病毒 A（RVA）是导致儿童和幼小动物急性病毒性肠胃炎的主要原因，但它的复制和发病机制仍不清楚。我们之前的研究表明，神经氨酸酶介导的末端唾液酸（SA）去除显著增强了 RVA-G9P[13]的复制，同时抑制了 RVA-G5P[7]的复制。在这项研究中，我们比较了猪回肠类器官（PIE）对 G5P[7]和 G9P[13]感染的转录组反应，重点关注与免疫反应、胆固醇代谢和宿主细胞附着相关的基因。分析表明，G9P[13]感染导致基因表达的强烈调节（4093 个显著调节基因与 G5P[7]调节的 488 个基因相比）和糖基转移酶编码基因的显著调节。两种毒株对与免疫反应相关的信号通路有不同的影响，G9P[13]主要上调，而 G5P[7]抑制这些通路。两种 RVAs 都调节了胆固醇转运蛋白编码基因的表达。G9P[13]而非 G5P[7]显著影响了神经酰胺合成途径，该途径已知会影响胆固醇和聚糖代谢。因此，我们的研究结果强调了调节细胞对新兴/重新出现和历史 RVA 株感染反应的独特机制，这些机制与 RVA-受体相互作用、代谢途径和免疫信号通路有关，对于设计有效的控制策略至关重要。
