Host Cell Response to Rotavirus Infection with Emphasis on Virus–Glycan Interactions, Cholesterol Metabolism, and Innate Immunity

Abstract

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.

Proteomic and phosphoproteomic profilings reveal distinct cellular responses during Tilapinevirus tilapiae entry and replication

“…Hence, studying virus-host cell interactions allows the impacts of viruses on host cellular regulation to be understood and provides insights into how host cells combat viral infections 41 . Generally, host cells respond to viral infections through a variety of mechanisms, such as immune activation, metabolic alteration, and cell cycle arrest, which demonstrates the dynamic nature of virus-host interactions 40,[42][43][44] . TiLV, a novel RNA virus identified in tilapia, can infect multiple fish cell lines and induce cell death across a range of tissues, including tilapia brain-, heart-, and liver-derived cell lines 33,[45][46][47][48] and other piscine cell lines 7,13,48 .…”

PoRVA G9P[23] and G5P[7] infections differentially promote PEDV replication by reprogramming glutamine metabolism

“…RVs are non-enveloped double-stranded RNA viruses that contain 11 segments of dsRNA encoding non-structural proteins (NSP1 to NSP5/6) and viral structural proteins (VP1 to VP4, VP6, and VP7). RVs are classified into 11 distinct groups, RV A-D F-L, which are further subdivided into distinct G/P genotypes based on the molecular characteristics of VP7 and VP4 [ 3 ]. Currently, RV A, B, C, and H have been identified in pigs; among them, RVA is considered the most common pathogenic RV species in pigs worldwide [ 4 , 5 ].…”