The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β
African swine fever virus (ASFV) poses serious threats to the swine industry. The mortality rate of African swine fever (ASF) is 100%, and there is no effective vaccine currently available. Complex immune escape strategies of ASFV are crucial factors affecting immune prevention and vaccine developme...
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2021
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oai:doaj.org-article:6b8466fe8b584615b5308d57a0ded50e2021-11-25T19:11:43ZThe African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β10.3390/vaccines91113712076-393Xhttps://doaj.org/article/6b8466fe8b584615b5308d57a0ded50e2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1371https://doaj.org/toc/2076-393XAfrican swine fever virus (ASFV) poses serious threats to the swine industry. The mortality rate of African swine fever (ASF) is 100%, and there is no effective vaccine currently available. Complex immune escape strategies of ASFV are crucial factors affecting immune prevention and vaccine development. CD2v and MGF360-505R genes have been implicated in the modulation of the immune response. The molecular mechanisms contributing to innate immunity are poorly understood. In this study, we discover the cytopathic effect and apoptosis of ΔCD2v/ΔMGF360-505R-ASFV after infection in porcine alveolar macrophages (PAMs) was significantly less than wild-type ASFV. We demonstrated that CD2v- and MGF360-505R-deficient ASFV decrease the level of apoptosis by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription. Compared with wild-type ASFV infection, the levels of phospho-NF-κB p65 and p-IκB protein decreased in CD2v- and MGF360-505R-deficient ASFV. Moreover, CD2v- and MGF360-505R-deficient ASFV induced less IL-1β production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. We further found that MGF360-12L, MGF360-13L, and MGF-505-2R suppress the promoter activity of NF-κB by reporter assays, and CD2v activates the NF-κB signaling pathway. These findings suggested that CD2v- and MGF360-505R-deficient ASFV could reduce the level of ASFV p30 and the apoptosis of PAMs by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription, which might reveal a novel strategy for ASFV to maintain the replication of the virus in the host.Qi GaoYunlong YangWeipeng QuanJiachen ZhengYizhuo LuoHeng WangXiongnan ChenZhao HuangXiaojun ChenRunda XuGuihong ZhangLang GongMDPI AGarticleAfrican swine fever virusMGFCD2vNF-κBIL-1βapoptosisMedicineRENVaccines, Vol 9, Iss 1371, p 1371 (2021) |
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African swine fever virus MGF CD2v NF-κB IL-1β apoptosis Medicine R |
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African swine fever virus MGF CD2v NF-κB IL-1β apoptosis Medicine R Qi Gao Yunlong Yang Weipeng Quan Jiachen Zheng Yizhuo Luo Heng Wang Xiongnan Chen Zhao Huang Xiaojun Chen Runda Xu Guihong Zhang Lang Gong The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β |
description |
African swine fever virus (ASFV) poses serious threats to the swine industry. The mortality rate of African swine fever (ASF) is 100%, and there is no effective vaccine currently available. Complex immune escape strategies of ASFV are crucial factors affecting immune prevention and vaccine development. CD2v and MGF360-505R genes have been implicated in the modulation of the immune response. The molecular mechanisms contributing to innate immunity are poorly understood. In this study, we discover the cytopathic effect and apoptosis of ΔCD2v/ΔMGF360-505R-ASFV after infection in porcine alveolar macrophages (PAMs) was significantly less than wild-type ASFV. We demonstrated that CD2v- and MGF360-505R-deficient ASFV decrease the level of apoptosis by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription. Compared with wild-type ASFV infection, the levels of phospho-NF-κB p65 and p-IκB protein decreased in CD2v- and MGF360-505R-deficient ASFV. Moreover, CD2v- and MGF360-505R-deficient ASFV induced less IL-1β production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. We further found that MGF360-12L, MGF360-13L, and MGF-505-2R suppress the promoter activity of NF-κB by reporter assays, and CD2v activates the NF-κB signaling pathway. These findings suggested that CD2v- and MGF360-505R-deficient ASFV could reduce the level of ASFV p30 and the apoptosis of PAMs by inhibiting the NF-κB signaling pathway and IL-1β mRNA transcription, which might reveal a novel strategy for ASFV to maintain the replication of the virus in the host. |
format |
article |
author |
Qi Gao Yunlong Yang Weipeng Quan Jiachen Zheng Yizhuo Luo Heng Wang Xiongnan Chen Zhao Huang Xiaojun Chen Runda Xu Guihong Zhang Lang Gong |
author_facet |
Qi Gao Yunlong Yang Weipeng Quan Jiachen Zheng Yizhuo Luo Heng Wang Xiongnan Chen Zhao Huang Xiaojun Chen Runda Xu Guihong Zhang Lang Gong |
author_sort |
Qi Gao |
title |
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β |
title_short |
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β |
title_full |
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β |
title_fullStr |
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β |
title_full_unstemmed |
The African Swine Fever Virus with MGF360 and MGF505 Deleted Reduces the Apoptosis of Porcine Alveolar Macrophages by Inhibiting the NF-κB Signaling Pathway and Interleukin-1β |
title_sort |
african swine fever virus with mgf360 and mgf505 deleted reduces the apoptosis of porcine alveolar macrophages by inhibiting the nf-κb signaling pathway and interleukin-1β |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/6b8466fe8b584615b5308d57a0ded50e |
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