Abstract

Rotavirus (RV) infection is one of the main pathogenic causes of severe gastroenteritis and diarrhea in infants and young animals. This study aimed to determine how dietary l-isoleucine supplementation improves the growth performance and immune response in weaned piglets with RV infection. In cell culture experiment, after IPEC-J2 and 3D4/31 cells were treated by 8 mM l-isoleucine for 24 h, the gene expressions of β-defensins and pattern recognition receptors (PRR) signaling pathway were significantly increased. Then, in the in vivo experiment, 28 crossbred weaned pigs were randomly divided into two groups fed with basal diet with or without l-isoleucine for 18 days. On the 15th day, the oral RV gavage was executed in the half of piglets. Average daily feed intake and gain of piglets were impaired by RV infection (P < 0.05). RV infection also induced severe diarrhea and the increasing serum urea nitrogen concentration (P < 0.05), and decreased CD4+ lymphocyte and CD4+/CD8+ ratio of peripheral blood (P < 0.05). However, dietary l-isoleucine supplementation attenuated diarrhea and decreasing growth performance (P < 0.05), decreased the NSP4 concentration in ileal mucosa, and enhanced the productions and/or expressions of immunoglobulins, RV antibody, cytokines, and β-defensins in serum, ileum, and/or mesenteric lymph nodes of weaned piglets (P < 0.05), which could be relative with activation of PRR signaling pathway and the related signaling pathway (P < 0.05) in the weaned pigs orally infused by RV. These results indicate that dietary l-isoleucine could improve the growth performance and immune function, which could be derived from l-isoleucine treatment improving the innate and adaptive immune responses via activation of PRR signaling pathway in RV-infected piglets. It is possible that l-isoleucine can be used in the therapy of RV infection in infants and young animals.

Highlights

  • Rotavirus (RV), a double-strained RNA virus of the family Reoviridae, is the main cause of severe diarrhea hospitalization among infants, and causing ~527,000 deaths per year worldwide [1,2,3]

  • Recently studies have shown that supplementing l-isoleucine can improve the health status and growth of human infants and young animals that were challenged by some pathogens via improving the immune function [10, 14, 18, 19]. l-Isoleucine treatment should improve the innate immunity possibly via some signaling pathways, such as TLRs, retinoic acid inducible gene I (RIG-I), mitochondrial antiviral-signaling protein (MAVS) and melanoma differentiation-associated protein 5 (MDA5), which can stimulate the generation and expression of anti-pathogen components

  • L-isoleucine treatment significantly stimulated the expressions of toll-like receptor 3 (TLR3), RIG-I, MDA5, MAVS, interferon regulatory factor 3 (IRF3), NF-κB, IFNβ, IFNγ, porcine beta-defensin 2 (pBD2), and/or pBD3 in IPEC-J2 and 3D4/31 cells

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Summary

Introduction

Rotavirus (RV), a double-strained RNA (dsRNA) virus of the family Reoviridae, is the main cause of severe diarrhea hospitalization among infants, and causing ~527,000 deaths per year worldwide (especially developing country) [1,2,3]. The previous study revealed that the replication of RV was restricted in the interferon (IFN)-treated cells [4], which indicates that IFN may play a vital role l-Isoleucine Administration Alleviates RV Infection in antiviral immune response. During the initial stage of RV infection, RV may suppress the expression of type I IFN and pro-inflammation cytokines through stimulating the proteasome-mediated degradation of IRF3 and NF-κB [4, 7, 8]. These may impair the antiviral immune response and lead to a severe gastroenteritis. Isoleucine has the capacity of preventing the invasion of pathogens via the increase of immunity

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