Negative regulation of type I interferon signaling by integrin-linked kinase permits dengue virus replication

Yi Sheng Kao, Li Chiu Wang, Po Chun Chang, Heng Ming Lin, Yee-Shin Lin, Chia Yi Yu, Chien Chin Chen, Chiou Feng Lin, Trai Ming Yeh, Shu Wen Wan, Jen Ren Wang, Tzong Shiann Ho, Chien Chou Chu, Bo Cheng Zhang, Chih Peng Chang

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κBdriven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection.

原文English
文章編號e1011241
期刊PLoS pathogens
19
發行號3 March
DOIs
出版狀態Published - 2023 3月

All Science Journal Classification (ASJC) codes

  • 寄生物學
  • 微生物學
  • 免疫學
  • 分子生物學
  • 遺傳學
  • 病毒學

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