The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1
Abstract HSV-2 is one of the most common sexually transmitted pathogens worldwide and HSV-2 infection triggers cytokine and chemokine production. However, little is known about which HSV-2 genes engage in the regulation of NF-κB signaling and what mechanisms are involved. In a screen of the unique s...
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Nature Portfolio
2017
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oai:doaj.org-article:00ce4a09013a41f488fefb97ebf1d6102021-12-02T16:06:40ZThe Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK110.1038/s41598-017-08856-42045-2322https://doaj.org/article/00ce4a09013a41f488fefb97ebf1d6102017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08856-4https://doaj.org/toc/2045-2322Abstract HSV-2 is one of the most common sexually transmitted pathogens worldwide and HSV-2 infection triggers cytokine and chemokine production. However, little is known about which HSV-2 genes engage in the regulation of NF-κB signaling and what mechanisms are involved. In a screen of the unique short (Us) regions of HSV-2, we observed that HSV-2 Us2 activates NF-κB signaling. We additionally indicated that deficiencies of Us2 decrease HSV-2 WT mediated NF-κB activation and cytokine and chemokine production, and overexpression of Us2 showed opposite effects. Co-immunoprecipitations indicated that Us2 interacted with TGF-β activated kinase 1 (TAK1), a serine/threonine kinase essential for NF-κB activation, and Us2 has the ability to regulate the TAK1-mediated pathway and induces TAK1 downstream signaling. Further studies verified that Us2 induced the phosphorylation of TAK1, resulting in the activation of TAK1 mediated downstream signaling. The role of Us2 in HSV-2 induced NF-κB pathways was also confirmed in the Us2-deficient mutant and HSV-2 WT infected mice. Our results indicate that HSV-2 Us2 gene product binds to TAK1 to positively regulate NF-κB signaling and, for the first time, provide insights into the molecular mechanism.Xuan LuChangjing HuangYi ZhangYong LinXueyu WangQian LiShi LiuJingfeng TangLi ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Xuan Lu Changjing Huang Yi Zhang Yong Lin Xueyu Wang Qian Li Shi Liu Jingfeng Tang Li Zhou The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1 |
| description |
Abstract HSV-2 is one of the most common sexually transmitted pathogens worldwide and HSV-2 infection triggers cytokine and chemokine production. However, little is known about which HSV-2 genes engage in the regulation of NF-κB signaling and what mechanisms are involved. In a screen of the unique short (Us) regions of HSV-2, we observed that HSV-2 Us2 activates NF-κB signaling. We additionally indicated that deficiencies of Us2 decrease HSV-2 WT mediated NF-κB activation and cytokine and chemokine production, and overexpression of Us2 showed opposite effects. Co-immunoprecipitations indicated that Us2 interacted with TGF-β activated kinase 1 (TAK1), a serine/threonine kinase essential for NF-κB activation, and Us2 has the ability to regulate the TAK1-mediated pathway and induces TAK1 downstream signaling. Further studies verified that Us2 induced the phosphorylation of TAK1, resulting in the activation of TAK1 mediated downstream signaling. The role of Us2 in HSV-2 induced NF-κB pathways was also confirmed in the Us2-deficient mutant and HSV-2 WT infected mice. Our results indicate that HSV-2 Us2 gene product binds to TAK1 to positively regulate NF-κB signaling and, for the first time, provide insights into the molecular mechanism. |
| format |
article |
| author |
Xuan Lu Changjing Huang Yi Zhang Yong Lin Xueyu Wang Qian Li Shi Liu Jingfeng Tang Li Zhou |
| author_facet |
Xuan Lu Changjing Huang Yi Zhang Yong Lin Xueyu Wang Qian Li Shi Liu Jingfeng Tang Li Zhou |
| author_sort |
Xuan Lu |
| title |
The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1 |
| title_short |
The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1 |
| title_full |
The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1 |
| title_fullStr |
The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1 |
| title_full_unstemmed |
The Us2 Gene Product of Herpes Simplex Virus 2 modulates NF-κB activation by targeting TAK1 |
| title_sort |
us2 gene product of herpes simplex virus 2 modulates nf-κb activation by targeting tak1 |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/00ce4a09013a41f488fefb97ebf1d610 |
| work_keys_str_mv |
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