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

• Main Authors: Quanyuan Wan, Zhiwei Liao, Youliang Rao, Chunrong Yang, Jianfei Ji, Xiaohui Chen, Jianguo Su
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: International Journal of Molecular Sciences
• Subjects: grass carp (<i>ctenopharyngodon idella</i>); gcrv; iron metabolism; <i>tfr1</i>; oxidative stress
• Online Access: https://www.mdpi.com/1422-0067/20/23/5857

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 (<i>Ctenopharyngodon idella</i>) 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 <i>C. idella</i> <i>transferrin receptor 1</i> (<i>CiTfR1</i>) rather than <i>transferrin</i> is upregulated upon GCRV infection. To clarify the implications of <i>CiTfR1</i> upregulation for antiviral immunity, we proved that <i>CiTfR1</i> 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 <i>CiTfR1</i> overexpression inhibited the mRNA expression of <i>C. idella interferon 1</i> (<i>CiIFN1</i>) and <i>CiIFN3</i>. The present study reveals a novel antiviral defense mechanism in teleost where <i>TfR1</i> 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.