2. Academic Validation
  3. Negative regulation of type I interferon signaling by integrin-linked kinase permits dengue virus replication

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

  • PLoS Pathog. 2023 Mar 17;19(3):e1011241. doi: 10.1371/journal.ppat.1011241.
Yi-Sheng Kao 1,  Li-Chiu Wang 2,  Po-Chun Chang 1,  Heng-Ming Lin 1,  Yee-Shin Lin 1 3 4,  Chia-Yi Yu 4 5,  Chien-Chin Chen 6 7,  Chiou-Feng Lin 8,  Trai-Ming Yeh 4 9,  Shu-Wen Wan 1 3 4,  Jen-Ren Wang 4 9,  Tzong-Shiann Ho 4 10,  Chien-Chou Chu 1,  Bo-Cheng Zhang 1,  Chih-Peng Chang 1 3 4
Affiliations

Affiliations

  • 1 Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 2 School of Medicine, I-Shou University, Kaohsiung, Taiwan.
  • 3 The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 4 Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
  • 5 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
  • 6 Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
  • 7 Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
  • 8 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 9 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 10 Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
PMID: 36930690 DOI: 10.1371/journal.ppat.1011241
Abstract

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-κB-driven 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.

Figures
Products