Transferrin Receptor 1-Associated Iron Accumulation and Oxidative Stress Provides a Way for Grass Carp to Fight against Reovirus Infection.

Quanyuan Wan,Chunrong Yang,Xiaohui Chen,Jianguo Su,Jianfei Ji,Youliang Rao,Zhiwei Liao

doi:10.3390/ijms20235857

Abstract

Iron is an essential element, closely linked with host immune responses. Nevertheless, the relationship between iron metabolism and virus infection is still unclear in aquatic vertebrates. To address this issue, we employed grass carp (Ctenopharyngodon idella) and its lethal virus, grass carp reovirus (GCRV), a double-strand RNA virus, as models. Our results demonstrate that GCRV infection increases the iron content and alters the expression of iron metabolism-related genes both in vivo and in vitro. Of note, the expression of C. idella transferrin receptor 1 (CiTfR1) rather than transferrin is upregulated upon GCRV infection. To clarify the implications of CiTfR1 upregulation for antiviral immunity, we proved that CiTfR1 was not a helper for GCRV invasion, but instead, it inhibited GCRV infection and promoted cell proliferation by facilitating the accumulation of intracellular labile iron pool (LIP), which increases intracellular oxidative stress. Interestingly, we found that CiTfR1 overexpression inhibited the mRNA expression of C. idella interferon 1 (CiIFN1) and CiIFN3. The present study reveals a novel antiviral defense mechanism in teleost where TfR1 induces the accumulation of LIP, leading to the suppression of virus infection and the proliferation of host cells, indicating that iron can be used as a medicated feed additive for the control of animal viral disease.

Highlights

To defend against the invasion of various pathogens, vertebrates are equipped with well-developed defensive systems: antibacterial or antiviral properties of tissue fluids and the phagocytic abilities of cells, known as the immune system including innate and adaptive immunity [1]
To verify that the intracellular oxidative stress caused by C. idella transferrin receptor 1 (CiTfR1) is associated with the iron accumulation in the cytoplasm, we further investigated the impact of iron on grass carp reovirus (GCRV) replication and intracellular oxidative stress in CIK cells
The present study aimed to identify the relationship between GCRV infection and iron metabolism in C. idella

Summary

Introduction

To defend against the invasion of various pathogens, vertebrates are equipped with well-developed defensive systems: antibacterial or antiviral properties of tissue fluids and the phagocytic abilities of cells, known as the immune system including innate and adaptive immunity [1]. The innate immune system, which is initiated by the recognition of pathogen-associated molecular patterns (PAMPs) through germline-encoded pattern-recognition receptors (PRRs), is the first line of host defense against invading pathogens [2]. Theses PAMP-activated PRRs can trigger a series of signaling cascades that rapidly induce the expression of a variety of cytokines involved in the inflammatory and immune responses. Nutrient limitation is another important immune response against the invasion of pathogens, which is termed nutritional immunity [3,4,5]

Methods

Results

Conclusion