SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS
The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is stil...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:46e6d4d9ac504d7da3bba21864a20ff62021-11-10T05:55:22ZSARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS1664-322410.3389/fimmu.2021.750969https://doaj.org/article/46e6d4d9ac504d7da3bba21864a20ff62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.750969/fullhttps://doaj.org/toc/1664-3224The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1β, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-κB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-κB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-κB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-κB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-κB signaling pathway.Weiling LiJialu QiaoQiang YouShan ZongQian PengYuchen LiuSong HuWei LiuShufen LiXiji ShuBinlian SunFrontiers Media S.A.articleSARS-CoV-2Nsp5MAVSSUMOylationNF-κBcytokineImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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DOAJ |
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DOAJ |
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SARS-CoV-2 Nsp5 MAVS SUMOylation NF-κB cytokine Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
SARS-CoV-2 Nsp5 MAVS SUMOylation NF-κB cytokine Immunologic diseases. Allergy RC581-607 Weiling Li Jialu Qiao Qiang You Shan Zong Qian Peng Yuchen Liu Song Hu Wei Liu Shufen Li Xiji Shu Binlian Sun SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS |
| description |
The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1β, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-κB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-κB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-κB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-κB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-κB signaling pathway. |
| format |
article |
| author |
Weiling Li Jialu Qiao Qiang You Shan Zong Qian Peng Yuchen Liu Song Hu Wei Liu Shufen Li Xiji Shu Binlian Sun |
| author_facet |
Weiling Li Jialu Qiao Qiang You Shan Zong Qian Peng Yuchen Liu Song Hu Wei Liu Shufen Li Xiji Shu Binlian Sun |
| author_sort |
Weiling Li |
| title |
SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS |
| title_short |
SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS |
| title_full |
SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS |
| title_fullStr |
SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS |
| title_full_unstemmed |
SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS |
| title_sort |
sars-cov-2 nsp5 activates nf-κb pathway by upregulating sumoylation of mavs |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/46e6d4d9ac504d7da3bba21864a20ff6 |
| work_keys_str_mv |
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| _version_ |
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