Duck HMGB2 Mediates Signaling Pathways in the Innate Immunity of Hosts Against Viral Infections.

Tingting Zhang,Xinyue Zhang,Liangmeng Wei,Zhenhong Sun,Xiaolan Hou,Gen Liu

doi:10.3389/fimmu.2020.572289

Abstract

High-mobility group box 2 (HMGB2) belongs to the HMG-box family that participates in a variety of biologic processes. Recent studies have suggested that HMGB2 plays an important role in the innate immunity of fish. Cherry Valley duck is the main duck bred for meat consumption in China, but there is limited research available on the impact of duck HMGB2 (duHMGB2) in antiviral innate immunity. Here, duHMGB2 genes were first cloned and analyzed from the spleen of Cherry Valley ducks. We show that duHMGB2 is widely distributed in most tissues of healthy ducks, and duHMGB2 was differentially expressed in three organs (the spleen, brain, and lung) of ducks during different viral infections. duHMGB2 is mainly expressed in the nucleus of duck embryo fibroblast (DEF) cells. However, duHMGB2 is released into the cytoplasm after viral infection. DuHMGB2 induced expression of several genes that regulate the immune response. Moreover, duHMGB2 activated and upregulatede transcription factor NF-κB promoter activity. We also used single gene manipulations (knockout or overexpression) to confirm that duHMGB2 can inhibit the replication of duck plague virus, duck Tembusu virus, and the novel duck reovirus in DEF cells. These data show that duHMGB2 can activate the antiviral innate immunity of the host. Thus, duHMGB2 may be considered an immune adjuvant against infectious diseases in duck.

Highlights

High-mobility group box 2 (HMGB2) belongs to the HMG-box family and its translated protein contains two HMG-box domains and a highly acidic C-terminal tail [1]. duck HMGB2 (duHMGB2) is a member of the highly conserved non-histone DNA-binding protein family [2]
The amino acid sequence of duHMGB2 was predicted and analyzed by SMART software, and it presented the typical structure of HMGBs: two functional domains that bind to DNA and an acidic C-terminus domain (183–202aa) (Figure 1B)
The phylogenetic tree shows that duHMGB2 has the highest homology with the Mallard and Prowl duck species predicted on NCBI and has lower homology with mammals and reptiles

Summary

Introduction

High-mobility group box 2 (HMGB2) belongs to the HMG-box family and its translated protein contains two HMG-box domains and a highly acidic C-terminal tail [1]. duHMGB2 is a member of the highly conserved non-histone DNA-binding protein family [2]. DuHMGB2 is a member of the highly conserved non-histone DNA-binding protein family [2]. Pattern recognition receptors (PRRs) are members of recognition molecules that are mainly located on the surface of innate immune cells and can recognize one or more pathogen-associated molecular patterns (PAMPs) [4]. Pattern recognition receptors such as toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like helicases (RLRs) are activated when pathogenic microorganisms invade the organism. The HMGB proteins function as universal sentinels for nucleic acids and recognize PRRs (discriminative sensing) to activate nucleic-acid-induced innate immune responses [7, 8]

Methods

Results

Conclusion