Bovine viral diarrhea virus NS4B protein interacts with 2CARD of MDA5 domain and negatively regulates the RLR-mediated IFN-ß production.

Bovine viral diarrhea virus (BVDV) is an important member of the family Flaviviridae and often causes immunosuppression. Previous studies have suggested that BVDV envelope protein Erns and the nonstructural autoprotease Npro can inhibit host innate immune responses. Herein, we found that BVDV NS4B, as a nonstructural protein necessary for replication, is involved in antagonizing the main RNA virus sensing pathway. Overexpression of BVDV NS4B protein significantly inhibited Sendai virus (SeV)-induced interferon-ß promoter activity, IFN-ß mRNA and IFN regulatory factor 3 (IRF3) phosphorylation levels. We also discovered that BVDV NS4B protein significantly inhibited RIG-I like receptor (RLRs)-mediated interferon-ß (IFN-ß) promoter activity and endogenous MDA5 mRNA levels. In addition, the BVDV NS4B protein directly interacts with N-terminal CARDs of MDA5, and co-localized with MDA5 or MDA5-2CARD in the cytoplasm. In summary, the results of this study indicate that the BVDV NS4B protein acts as an interferon-ß antagonist through inhibiting the MDA5-mediated signal transduction pathway. Our study provides an in-depth understanding of the molecular mechanisms of BVDV evading the host's natural immune response.

Advances in neoadjuvant therapy of esophageal cancer involved in organ preservation / 国际肿瘤学杂志

Esophageal squamous cell carcinoma is one of the most common cancer in China, and locally advanced stage remains a heterogeneous and complex disease. Its treatments are constantly evolving. To date, radiochemotherapy and surgery are involved in the comprehensive treatment of this disease. However, because of the specifical anatomical location of esophagus, its physiological function will be impaired after surgical resection. If similar survival is obtained in esophageal cancer, an organ preserving strategy without surgery is of great significance for improving the quality of life. As a non-invasive tumor treatment method, neoadjuvant therapy plays an important role in the comprehensive treatment of preserving the esophagus. Recently, there are studies investigating the role of organ preserving strategy in the comprehensive treatment of esophageal cancer with neoadjuvant therapy, and the recognition of these advances will provide reference value for the comprehensive treatment of esophageal cancer.