S6. impaired antiviral immune response. Mechanistically, NDR2 directly associates with RIG-I and TRIM25, thus facilitating the RIG-I/TRIM25 complex and enhancing the ICAM3 TRIM25-mediated K63-linked polyubiquitination of RIG-I, which is required for the RIG-ICmediated antiviral immune response. Furthermore, NDR2 expression is notably down-regulated in peripheral blood from respiratory syncytial virusCinfected patients and in virus-infected macrophages. Collectively, these findings provide insights into the function of NDR2 in antiviral immunity and its related clinical significance. INTRODUCTION The innate immune system functions as the frontier of host defense to sense and fight against microbial pathogen invasion via recognition of pathogen-associated molecular patterns aided by pattern recognition receptors (PRRs) ((((and PMs infected with VSV in K 858 the indicated times was detected by enzyme-linked immunosorbent assay (ELISA) (A) and real-time polymerase chain reaction (PCR) analysis (B). (C) Real-time PCR analysis of IFN-, IL-6, and TNF- transcripts in and PMs treated with phosphate-buffered saline (PBS) or with the infection of H1N1, K 858 SeV, RSV, EMCV, HSV-1, or MHV68 for 8 hours. (D) Fluorescence-activated cell sorting (FACS) analysis of enhanced green fluorescent protein (eGFP) fluorescence intensity in and PMs infected with VSV-eGFP. (E) VSV-eGFP titers by TCID50 assay in supernatants of and PMs infected with VSV-eGFP for 6 hours. (F) and PMs were transfected with empty vector (mock), NDR2, or its kinase-inactive mutants overexpressing plasmids for 36 hours and then infected with VSV, followed by real-time PCR analysis of IFN-, IL-6, and TNF- expression. AA, K282A/T442A. (G) FACS analysis of RAW264.7 cells stably overexpressing NDR2 or its kinase-inactive mutants infected with VSV-eGFP. Data are means SD and are representative of three independent experiments. Students test was used for statistical calculation. ns, no significance. * 0.05, ** 0.01, and *** 0.001. As a protein kinase, NDR2 reportedly phosphorylates different substrates to influence a variety of biological processes, including ciliogenesis, neurite formation, and cell survival (and mice (= 6 per group) 12 hours after intraperitoneal infection with VSV [1 107 plaque-forming units (PFU) g?1]. (B) VSV titers by TCID50 assay in spleens, lungs, and livers from mice in (A). (C) Pathology of and mice in response to VSV infection. Hematoxylin and eosin staining of lung sections from mice in (A). Scale bars, 200 m (for 4) and 50 m (for 20). (D) Neutrophil (CD11b+Gr-1+) infiltration in murine bronchoalveolar lavage K 858 fluid (BALF) from mice treated with intraperitoneal injections of PBS (= 3) or VSV (1 107 PFU g?1 and = 3) was assessed 12 hours after injection. (E) Survival of 8-week-old male and mice administered VSV (1 108 PFU g?1) via tail intravenous injection (= 8 per group; Wilcoxon test). (F) Survival curve for 8-week-old male (= 8) and (= 9) mice infected with H1N1 virus (2 103 PFU per mouse) by intranasal inoculation (Wilcoxon test). (G) Real-time PCR analysis of flu-M mRNA of lungs from 8-week-old male and mice 4 days after intranasal inoculation with H1N1 virus (2 103 PFU per mouse) (= 6 per group). Data are means SD and are representative of three independent K 858 experiments. Students test was used for statistical calculation. * 0.05, ** 0.01, and *** 0.001. NDR2 promotes virus-triggered signaling at the RIG-I level.
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- Post author:aftaka
- Post published:October 4, 2024
- Post category:Cytochrome P450