Molecular Biomedicine Department, Margarita Salas Center for Biological Research (CIB-CSIC), Madrid, Spain.
Department of Genetics, Immunogenomics and Molecular Pathogenesis Group, UIC Zoonoses and Emergent Diseases ENZOEM, University of Córdoba, Córdoba, Spain.
Front Immunol. 2023 Jul 20;14:1220306. doi: 10.3389/fimmu.2023.1220306. eCollection 2023.
SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both and were significantly up-regulated in A549 cells expressing individual accessory proteins ORF6, ORF8, ORF9b or ORF9c from SARS-CoV-2 (Wuhan-Hu-1 isolate). IL11 is a member of the IL6 family of cytokines. IL11 signaling-related genes were also differentially expressed. Bioinformatics analysis disclosed that both and were involved in pulmonary fibrosis idiopathic disease and functional assays confirmed their association with profibrotic cell responses. Subsequently, data comparison with lung cell lines infected with SARS-CoV-2 or lung biopsies from patients with COVID-19, evidenced altered profibrotic gene expression that matched those obtained in this study. Our results show ORF6, ORF8, ORF9b and ORF9c involvement in inflammatory and profibrotic responses. Thus, these accessory proteins could be targeted by new therapies against COVID-19 disease.
导致 COVID-19 大流行的 SARS-CoV-2 在其基因组中编码了十一种辅助蛋白。它们在感染过程中的作用仍不完全清楚。在这项研究中，转录组学分析显示，在表达来自 SARS-CoV-2（武汉-Hu-1 分离株）的单个辅助蛋白 ORF6、ORF8、ORF9b 或 ORF9c 的 A549 细胞中， 和 均显著上调。IL11 是细胞因子 IL6 家族的一员。IL11 信号相关基因也表现出差异表达。生物信息学分析表明， 和 均参与特发性肺纤维化疾病，功能测定证实它们与促纤维化细胞反应有关。随后，将这些数据与感染 SARS-CoV-2 的肺细胞系或 COVID-19 患者的肺活检进行比较，结果表明，纤维化基因的表达发生了改变，与本研究中获得的结果相匹配。我们的结果表明 ORF6、ORF8、ORF9b 和 ORF9c 参与了炎症和促纤维化反应。因此，这些辅助蛋白可能成为针对 COVID-19 疾病的新疗法的靶点。
