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Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type Ⅰ interferon signaling by targeting STAT1

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机构: [1]Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan, 650224, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan, 650223, China. Electronic address: lizhuoran85@126.com. [2]NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China. [3]Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan, 650224, China. [4]Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA. [5]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan, 650223, China. Electronic address: zhengyt@mail.kiz.ac.cn. [6]Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan, 650224, China. Electronic address: li_huachun@hotmail.com.
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关键词: Bluetongue virus Interferon Non-structural protein Phosphorylation STAT1

摘要:
Previous studies have pointed out that bluetongue virus (BTV) down-regulates the expression levels of type Ⅰ interferon (IFN-Ⅰ) and inhibits IFN-Ⅰ signaling by targeting on the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription protein (STAT) pathway. However, individual viral protein could not effectively block IFN-Ⅰ signaling. There is a need to explore the underlying mechanisms by which viral proteins of BTV coordinate to antagonize the IFN-Ⅰ signaling. We investigated the coordinative role of BTV-1 nonstructural protein 3 (NS3) and NS4 in counteracting IFN-Ⅰ signaling in the JAK-STAT pathway by directly interacting with STAT1. The NS3 and NS4 targeted the SH2 domain of STAT1 to inhibit its phosphorylation, heterodimerization, nuclear translocation, as well as activation of downstream genes of the JAK-STAT pathway. NS3 and NS4 impaired STAT1 phosphorylation induced by IFN-Ⅰ in a dose dependent manner. Overall, this study confirmed that NS3 and NS4 of BTV participate in interfering with IFN-Ⅰ signaling process. Also, a new mechanism employed by BTV to evade host innate immune responses was revealed. © 2021 Elsevier B.V.

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出版当年[2022]版:
大类 | 2 区 农林科学
小类 | 2 区 兽医学 3 区 微生物学
最新[2023]版:
大类 | 2 区 农林科学
小类 | 1 区 兽医学 3 区 微生物学
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出版当年[2021]版:
Q1 VETERINARY SCIENCES Q3 MICROBIOLOGY
最新[2023]版:
Q1 VETERINARY SCIENCES Q3 MICROBIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan, 650224, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan, 650223, China. Electronic address: lizhuoran85@126.com.
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通讯机构: [1]Yunnan Tropical and Subtropical Animal Virus Diseases Laboratory, Yunnan Animal Science and Veterinary Institute, Kunming, Yunnan, 650224, China; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan, 650223, China. Electronic address: lizhuoran85@126.com. [4]Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
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