African Swine Fever Virus F317L Protein Inhibits NF-κB Activation To Evade Host Immune Response and Promote Viral Replication

Yang, Jinping; Li, Shasha; Tian, Feng; Zhang, Xiangle; Yang, Fan; Cao, Weijun; Chen, Hongjun; Liu, Huisheng; Zhang, Keshan; Zhu, Zixiang; Zheng, Haixue

doi:10.1128/msphere.00658-21

Cited by 49 publications

(38 citation statements)

References 42 publications

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“…pF317L consists of 317 amino acids, and its function is still unknown ( Dixon et al., 2013 ). A recent report shows that pF317L is an inhibitor of the inflammatory responses ( Yang et al., 2021 ). pF317L inhibits TNFα and poly(dA:dT)-induced proinflammatory cytokine expression and NF-κB promoter activation.…”

Section: Escape From Innate Immunitymentioning

confidence: 99%

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Regulation of antiviral immune response by African swine fever virus (ASFV)

2022

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Section: Escape From Innate Immunitymentioning

confidence: 99%

“…Naturally, p317L also inhibits p65 nuclear translocation. It is found that the amino acids from 109 to 208 in pF317L are critical for its interaction with IKKβ and the suppression of NF-κB activation ( Yang et al., 2021 ). Importantly, deletion of F317L from ASFV is lethal to the virus.…”

Section: Escape From Innate Immunitymentioning

confidence: 99%

Regulation of antiviral immune response by African swine fever virus (ASFV)

2022

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“…In 2020, Zhuo et al demonstrated that MGF360-12L can block the interaction between p65 and KPNA2, KPNA3, and KPNA4, and can interfere with the nuclear translocation of NF-κB [ 43 ]. Five immunosuppressive genes were reported in 2021, including E120R, F317L, MGF505-7R, MGF505-11R, and I215L [ 44 , 45 , 46 , 47 , 48 , 49 ]. E120R can interact and block the activation of IRF3, thereby inhibiting the expression of IFN-β [ 44 ].…”

Section: The Major Defense Mechanisms and Asfv Interactionsmentioning

confidence: 99%

“…E120R can interact and block the activation of IRF3, thereby inhibiting the expression of IFN-β [ 44 ]. F317L inhibits IKKβ phosphorylation, thereby reducing the phosphorylation and ubiquitination of IkBα, thereby inhibiting the activation of the NF-κB pathway [ 45 ]. Li et al reported that MGF-505-7R promoted the expression of autophagy-related protein ULK1 to degrade STING, and inhibited IFN-γ-mediated JAK1 and JAK2-mediated signaling pathways [ 46 , 48 ].…”

Section: The Major Defense Mechanisms and Asfv Interactionsmentioning

confidence: 99%

Immune Escape Mechanism and Vaccine Research Progress of African Swine Fever Virus

Wang

Huang

et al. 2022

Vaccines

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African swine fever virus (ASFV) is the causative agent of the epidemic of African swine fever (ASF), with virulent strains having a mortality rate of up to 100% and presenting devastating impacts on animal farming. Since ASF was first reported in China in 2018, ASFV still exists and poses a potential threat to the current pig industry. Low-virulence and genotype I strains of ASFV have been reported in China, and the prevention and control of ASF is more complicated. Insufficient understanding of the interaction of ASFV with the host immune system hinders vaccine development. Physical barriers, nonspecific immune response and acquired immunity are the three barriers of the host against infection. To escape the innate immune response, ASFV invades monocytes/macrophages and dendritic cells, thereby inhibiting IFN expression, regulating cytokine expression and the body’s inflammatory response process. Meanwhile, in order to evade the adaptive immune response, ASFV inhibits antigen presentation, induces the production of non-neutralizing antibodies, and inhibits apoptosis. Recently, significant advances have been achieved in vaccine development around the world. Live attenuated vaccines (LAVs) based on artificially deleting specific virulence genes can achieve 100% homologous protection and partial heterologous protection. The key of subunit vaccines is identifying the combination of antigens that can effectively provide protection and selecting carriers that can effectively deliver the antigens. In this review, we introduce the epidemic trend of ASF and the impact on the pig industry, analyze the interaction mechanism between ASFV and the body’s immune system, and compare the current status of potential vaccines in order to provide a reference for the development of effective ASF vaccines.

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“…A528R inhibits TLR8-NF-kB signaling by targeting p65 activation and nuclear translocation (Liu X. et al, 2021). F317L interacts with IkB kinase b (IKKb) and impairs NF-kB pathway activation by disrupting NF-kB activity to evade the host immune response (Yang J. et al, 2021). ASFV MGF360-14L has been selected as target gene of deletion for attenuated ASF vaccine development, yet its function is still unclear.…”

Section: Introductionmentioning

confidence: 99%

African Swine Fever Virus MGF360-14L Negatively Regulates Type I Interferon Signaling by Targeting IRF3

Wang

Cui

Xin

et al. 2022

Front. Cell. Infect. Microbiol.

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African swine fever (ASF) is a devastating infectious disease caused by African swine fever virus (ASFV). The ASFV genome encodes multiple structural and non-structural proteins that contribute to evasion of host immunity. In this study, we determined that the viral non-structural protein MGF360-14L inhibits interferon-β (IFN-β) promoter activity induced by cGAS-STING signaling. MGF360-14L was also found to downregulate expression of the IRF3 protein and promote its degradation through ubiquitin-meditated proteolysis. Moreover, MGF360-14L was shown to interact with and destabilize IRF3 by facilitating E3 ligase TRIM21-mediated K63-linked ubiquitination of IRF3. Overall, our study revealed that MGF360-14L promotes degradation of IRF3 through TRIM21, thereby inhibiting type I interferon production. These findings provide new insights into the mechanisms underlying ASFV immune evasion.

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African Swine Fever Virus F317L Protein Inhibits NF-κB Activation To Evade Host Immune Response and Promote Viral Replication

Cited by 49 publications

References 42 publications

Regulation of antiviral immune response by African swine fever virus (ASFV)

Regulation of antiviral immune response by African swine fever virus (ASFV)

Immune Escape Mechanism and Vaccine Research Progress of African Swine Fever Virus

African Swine Fever Virus MGF360-14L Negatively Regulates Type I Interferon Signaling by Targeting IRF3

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