TRIM Family Of Proteins: TRIM22, TRIM14 Inhibits The Function And Mechanism Of Influenza Virus

Influenza viruses pose a serious threat to public health which can result in severe diseases and even death in vulnerable and high-risk populations. Influenza epidemics are estimated to contribute to about 3 million to 5 million cases of serious diseases and about 250 thousand to 500 thousand cases of death worldwide each year. It is demonstrated that influenza viruses are divided into type A, B, and C on the basis of variation in the nucleoprotein antigen, in which influenza A virus (IAV) is the most common infectious pathogen. There is currently a lack of effective drug treatment for influenza since the virus can evolve resistance to drugs. Although virus infection can be prevented by the vaccine, the annual epidemic strains of influenza viruses are different and found to be highly mutated. Therefore, preventing infection only by injecting vaccine is not enough. Therefore, there is a very urgent need to find new mechanisms for the inhibition of influenza virus, which may provide clues for the development of new drugs.Interferon plays a prominent role when the innate immunity fights against the infection of influenza virus, and induces the expression of ISG (interferon-stimulated gene) which inhibits the replication of the virus by changing cell metabolism and internal environment, or directly interacting with virus. The ISG includes a number of TRIM proteins. The TRIM (tripartite motif) family proteins, characterized by the presence of the tripartite motif, are composed of a RING domain, one or two B-box domain(s) and a Coiled-coil region. TRIM 14 and TRIM22 are members of TRIM family.Recently, some TRIM proteins have been identified as inhibitors of viruses such as HBV, HIV, IAV and so on. However, the relationship between TRIM 14 and influenza viruses is still unclear.TheTRIM22 isdesigned as the research objectto verify whether BiLC system can quickly and effectively detect the protein-protein interactions between ISGs and influenza viruses.In addition, methods have been constructed to produce stable expression of cell line and a system to detect the replication of the influenza virus has also been set up. Consistent with the results reported in the literature, TRIM22 can effectively inhibit the replication of influenza viruses and interact with NP proteins. And this paperis aiming to study the relationship between TRIM 14 and influenza viruses. It has been discovered that TRIM14 can be induced by interferon and influenza virus in A549 cells. Furthermore, the viral amplification experiments with TRIM14 over-expressing cells and KO TRIM 14 cells have proved that TRIM 14 is an inhibitor of influenza viral replication. Further studies indicate that the interaction between TRIM14 and NP, M2, NS1, PA is of vital importance to inhibit IAV.All the significance of this thesis is to provide a new approach to make quick research on the relationship between ISGs and influenza virus. Besides, this study enriches the content of the mechanism for the inhibition of influenza virus. In the meantime, a new perspective is brought to develop new drugs.