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TLR4 TIR domain and nucleolin GAR domain synergistically mediate RSV infection and induce neuronal inflammatory damage in SH-SY5Y cells.
Jiang, Chengcheng; Huang, Yixuan; Gui, Hongya; Liu, Xiaojie; Li, Haiwen; Han, Maozhen; Huang, Shenghai.
Afiliación
  • Jiang C; Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
  • Huang Y; Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • Gui H; Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
  • Liu X; Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
  • Li H; Department of Gastroenterology, the Third Affiliated Hospital of Anhui Medical University, Hefei First People's Hospital, Hefei, Anhui, China.
  • Han M; School of Life Sciences, Anhui Medical University, Hefei, Anhui, China.
  • Huang S; Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China.
J Med Virol ; 96(4): e29570, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38558098
ABSTRACT
Previous research results of our group showed that Toll-like receptor 4 (TLR4) and nucleolin synergistically mediate respiratory syncytial virus (RSV) infection in human central neuron cells, but the specific mechanism remains unclear. Here we designed and synthesized lentiviruses with TIR (674-815 aa), TLR4 (del 674-815 aa), GAR (645-707 aa), and NCL (del 645-707 aa) domains, and obtained stable overexpression cell lines by drug screening, and subsequently infected RSV at different time points. Laser confocal microscopy and coimmunoprecipitation were used for the observation of co-localization and interaction of TIR/GAR domains. Western blot analysis was used for the detection of p-NF-κB and LC3 protein expression. Real-time PCR was used for the detection of TLR4/NCL mRNA expression. ELISA assay was used to measure IL-6, IL-1ß, and TNF-α concentrations and flow cytometric analysis was used for the study of apoptosis. Our results suggest that overexpression of TIR and GAR domains can exacerbate apoptosis and autophagy, and that TIR and GAR domains can synergistically mediate RSV infection and activate the NF-κB signaling pathway, which regulates the secretion of downstream inflammatory factors, such as IL-6, IL-1ß, and TNF-α, and ultimately leads to neuronal inflammatory injury.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por Virus Sincitial Respiratorio / Neuroblastoma Límite: Humans Idioma: En Revista: J Med Virol Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Infecciones por Virus Sincitial Respiratorio / Neuroblastoma Límite: Humans Idioma: En Revista: J Med Virol Año: 2024 Tipo del documento: Article País de afiliación: China