Dynamic Proteomics Study On The Interactions Between Influenza A Virus And Host Cells

Influenza A viruses(IAVs) are negative-sense, single-stranded, segmented RNA viruses. IAVs can cause a human and animal influenza pandemic, which is a serious threat to human health. Influenza A viruses infect the host cells through a series of processes, such as replication and reproduction. However, these processes are complicated, in which a variety of proteins from host and virus are involved. Besides, the mechanisms underlining the interaction between the influenza virus and host still remain unclear. Additionally, IAVs mutate constantly. All these facts pose great challenges to drug development, human disease prevention and control over the influenza A virus. So, an efficient and accurate research method is vital for better understanding the interaction mechanism between virus and host and accelerating drug research. First, using the nucleoprotein from H7N9 virus, we used coimmunoprecipitation coupled with mass spectrometry to enrich and detect a series of host proteins that may interact with nucleoprotein. 132 NP-related host proteins were identified by analyzing a large amount of data, of which 17 proteins were found to be involved in spliceosome signaling pathways. The result implied that nucleoprotein may be involved in the host cell in response to infection via the interaction with spliceosome pathways. Because co- immunoprecipitation used in this study is not suitable for high-throughput analysis. Thus, an alternative method to study the interaction between host with IAVs was adopted, which combines both the concept and the strategies of chemical biology with proteomic analysis technology. The newly synthesized proteins at the individual time points in host cell infected by H1N1 can be enriched and detected by the specific chemical molecular probe through bioorthogonal reaction. The minor alterations of host proteome caused by the infection of influenza virus can be profiled, through a method with high-throughput and high accuracy. Through interpretation of the mass spectrometry data, we found that 2859 host proteins with differential expression have been identified during the process of H1N1 infection. The dataprovided a lot of useful information about the interaction between influenza A virus and host. A new method for subsequent studies has been established.The main purpose of this study was to clarify the molecular mechanism of escaping immune surveillance for persistent infection about influenza A virus, and figure out how IAVs to destroy the host. Thus, this research has very important practical significance for discovering the new therapeutic targets and prevention measures.