Introduction

Rotavirus (RV) infection is the most common cause of severe gastroenteritis and the associated mortality in infants and young children and animals worldwide [1, 2]. Species A RV (RVA) was historically considered to be the most prevalent and pathogenic RV species, associated with > 90% of RV gastroenteritis cases [3]. However, there is growing evidence that species C RV (RVC) is a significant cause of infectious diarrhea in humans and animals [4,5,6,7]. While RVAs mostly affect piglets or young children after weaning [8, 9], RVC diarrhea is highly prevalent among nursing, 1–10-day-old piglets, causing significant economic losses to farmers and the pork industry [4, 10, 11]. Recent data suggest that reassortant RVC strains circulate in northeast Asia in both the human and swine populations [12]. In contrast to RVAs, most attempts to isolate or serially propagate RVCs of human or animal origin in continuous or primary cell lines were unsuccessful [13]. The lack of robust cell culture system has limited the ability to study RVC pathogenesis, immunity and to develop or evaluate vaccination/therapeutic approaches. Thus, there is an urgent need in identification of host factors associated with the limited ability of RVC to replicate in vitro.

The main targets for RV infection are mature enterocytes – absorptive intestinal epithelial cells (IECs) located at the tips of intestinal villi [14]. Several molecules on enterocytes and other IECs such as integrins [15], sialic acids (SAs) [16], gangliosides [17], N- and O-glycans [Full size image

All glycosyltransferase (with the exception of sialyltransferase) -encoding genes involved in ceramide biosynthesis (Fig. 10, Additional file 1) were significantly upregulated following infection with the two sialidase-dependent strains (G9P[13] and RVC).

Fig. 10
figure 10

Modulation of expression of genes encoding glycosyltransferases catalyzing the ganglioside biosynthesis in PIEs infected with RVC, G9P[13] and G5P[7] versus control (non-infected PIEs). Bars indicate fold change difference between infected PIEs versus uninfected control. Blue circles represent the significance (p-value < 0.05, i.e. 1.3 in − log10 format). Red boxes represent genes whose expression was not detected

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The unique downregulating effect of G9P[13] and RVC infection on the expression of sialyltransferase-encoding genes led us to further analyze the expression of genes associated with SA biosynthesis/degradation (Table 1, Additional file 1). Similar to the modulation of sialyltransferase-encoding genes, infection with G9P[13] and RVC downregulated the expression of SA biosynthesis-encoding genes. More specifically, both aforementioned viruses downregulated the expression of NANP gene encoding N-acylneuraminate 9-phosphatase responsible for dephosphorylation of sialic acid 9-phosphate to free sialic acid [47]. RVC infection also led to downregulation of expression of gene encoding N-acetylneuraminic acid 9-phosphate synthase (Neu5Ac-9-P synthase) which catalyses the primary synthesis of the most common sialic acid, N-acetylneuraminic acid (Neu5Ac, NeuNAc, or NeuAc) and SLC35A1 – gene encoding SA transporter—a transmembrane protein moving SA produced in nucleus into the Golgi apparatus, where SA is used as a substrate for sialylation by sialyltransferases [48, 49]. While no significant effect on this gene expression was observed in PIEs infected with G9P[13], infection with this virus led to downregulation of expression of NAGK-encoding gene whose product provides the conversion of GlcNAc to GlcNAc-6-phosphate [50]. In addition, G9P[13] and RVC infection significantly upregulated the expression of genes encoding proteins associated with SA catabolism with the most prominent change in expression of the gene encoding RENBP enzyme known for its catabolic role in SA metabolism [51]. Similar effect of these viruses was observed for the expression of gene encoding NEU1—sialidase which removes terminal SA from glycans [52]. In addition, G9P[13] infection was associated with downregulation of another catalytic enzyme—NPL. In contrast, no prominent change of genes encoding enzymes responsible for SA biosynthesis/degradation was observed in PIEs infected with G5P[7].

Table 1 Modulation of expression of genes associated with SA metabolism in PIEs infected with RVC, G9P[13] and G5P[7]
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