Effects of the NF-κB Signaling Pathway Inhibitor BAY11-7082 in the Replication of ASFV

Qi Gao,Jiachen Zheng,Runda Xu,Weipeng Quan,Xiongnan Chen,Guihong Zhang,Heng Wang,Zhao Huang,Yizhuo Luo,Xiaojun Chen,Yunlong Yang,Lang Gong,Yongzhi Feng

doi:10.3390/v14020297

Abstract

African swine fever virus (ASFV) mainly infects the monocyte/macrophage lineage of pigs and regulates the production of cytokines that influence host immune responses. Several studies have reported changes in cytokine production after infection with ASFV, but the regulatory mechanisms have not yet been elucidated. Therefore, the aim of this study was to examine the immune response mechanism of ASFV using transcriptomic and proteomic analyses. Through multi-omics joint analysis, it was found that ASFV infection regulates the expression of the host NF-B signal pathway and related cytokines. Additionally, changes in the NF-κB signaling pathway and IL-1β and IL-8 expression in porcine alveolar macrophages (PAMs) infected with ASFV were examined. Results show that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8. The NF-κB inhibitor BAY11-7082 inhibited the expression profiles of phospho-NF-κB p65, p-IκB, and MyD88 proteins, and inhibited ASFV-induced NF-κB signaling pathway activation. Additionally, the results show that the NF-κB inhibitor BAY11-7082 can inhibit the replication of ASFV and can inhibit IL-1β and, IL-8 expression. Overall, the findings of this study indicate that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8, and inhibits the replication of ASFV by inhibiting the NF-κB signaling pathway and interleukin-1 beta and interleukin-8 production. These findings not only provide new insights into the molecular mechanism of the association between the NF-κB signaling pathway and ASFV infection, but also indicate that the NF-κB signaling pathway is a potential immunomodulatory pathway that controls ASF.

Highlights

African swine fever (ASF) is an acute and highly infectious disease of pigs caused by African swine fever virus (ASFV), and is transmitted by domestic pigs, wild boars, and insect vectors [1]
In-depth research on the immune response and pathogenic mechanisms of ASFV-infected hosts is of great significance for the development of effective ASF vaccines and antiviral drugs
A previous study reported that five tissues—lung, spleen, liver, kidney, and lymph nodes—synergistically responded to ASFV infection and resisted ASFV through inflammatory cytokine storms and interferon activation, through transcriptomic and proteomic analysis [34]

Summary

Introduction

African swine fever (ASF) is an acute and highly infectious disease of pigs caused by African swine fever virus (ASFV), and is transmitted by domestic pigs, wild boars, and insect vectors [1]. The first ASFV case in China was reported on August 3, 2018, and it subsequently spread throughout the country within a few months. ASFV is highly restricted to porcine cells of the monocyte/macrophage lineage and preferentially infects porcine alveolar macrophages (PAMs) [4]. Acute infection of pigs with ASFV can result in up to 100% mortality. Virulent isolates of ASFV often cause a peracute to acute disease progression with high fever (>41 ◦C) and a range of clinical signs, including anorexia and lethargy, which occur within a few days of infection [7]. The genome of ASFV encodes nearly 200 proteins, of which more than 50 structural proteins are packaged into virus particles, which play an important role in the infection stage of the virus and participate in the process of genome replication and viral infection [9]

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