Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells.

Lin Yang,Si Chen,Linzhu Ren,Weilong Ji,Hongsheng Ouyang,Guyu Niu,Xiaohua Liu,Xue Li,Liying Zhang,Xinwei Zhang

doi:10.3390/v14010156

Abstract

Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues and plays an important role in systemic autoimmunity. However, TRIM21 plays different roles in different virus infections. In this study, we evaluate the relationship between porcine TRIM21 and PCV2 infection as well as host immune responses. We found that PCV2 infection modulated the expression of porcine TRIM21. TRIM21 can enhance interferons and proinflammatory factors and decrease cellular apoptosis in PCV2-infected cells. These results indicate that porcine TRIM21 plays a critical role in enhancing PCV2 infection, which is a promising target for controlling and developing the treatment of PCV2 infection.

Highlights

Porcine circovirus 2 (PCV2) is the pathogen causing porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are prevalent in almost all pig farms worldwide and considered one of the most important infectious diseases causing immunosuppression in pigs
We previously found by RNA-Seq analysis that several porcine tripartite motif proteins (TRIMs) expressed significantly differently in PCV2-infected cells
Higgs and colleagues found that Tripartite motif protein 21 (TRIM21) negatively regulates IFN-β production by polyubiquitin-mediated degradation of IRF3 in Sendai virus- and Japanese encephalitis virus-infected cells [31,40], while TRIM21 can promote the production of IFN-β by enhancing the dimerization and phosphorylation of IRF3 in Coxsackievirus B3 (CBV3)-infected cells, restricting CBV3 replication [29]

Summary

Introduction

Porcine circovirus 2 (PCV2) is the pathogen causing porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are prevalent in almost all pig farms worldwide and considered one of the most important infectious diseases causing immunosuppression in pigs. PCV2 interacts with the host proteins and replicates with the host component [1,2]. Intracellular host restriction factors, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), complement component 1Q subcomponent-binding protein (C1QBP), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein (14-33β/α, YWHAB), play important roles in resisting virus infection [1,2,12,13,14]. Among the intracellular host factors, tripartite motif proteins (TRIMs) are a kind of newly discovered host protein involved in various cellular functions, including cell cycles, immunity, carcinogenesis, apoptosis, as well as virus infection [15,16,17]. The B-box domain exists only in TRIM protein and is a cysteine-histidine-zinc finger motif, which mainly mediates the oligomerization of homologous or heterologous protein, promoting the formation of macromolecular and subcellular location. The C-terminal domain of the TRIM protein is a hypervariable region, which is the main domain of protein–protein interaction, and most TRIM proteins have a PRY/SPRY domain at the C-terminal [20,21]

Methods

Results

Conclusion