Identification And Functional Study Of Host Factor Associating With Influenza Virus Polymerase Basic Protein 1

Influenza is an important zoonosis and has caused huge impact on the stock farming and the public health.Influenza A virus(IAV)can infect several hosts and propagate in the hosts' cell.The viral ribonucleoprotein complex(vRNP)is the minimal transcriptional and replicative unit of IAV.The core part of vRNP is RNA-dependent RNA polymerase(RdRp),which is a heterotrimeric complex composed of polymerase basic protein 1(PB1),polymerase basic protein 2(PB2)and polymerase acidic protein(PA).The RdRp plays critical roles in the transcription and replication of IAV.PB1 is the core protein of the polymerase.PB1 subunit contains the conserved motif characteristics of RdRp,possessing the polymerase activity,being able to participate in the extension of the RNA strand.In addition,PB1 can bind to the vRNA and cRNA.For its replication in the infected cell,IAV need to utilize multiple host factors,some host factors play an important role in the proliferation of IAV.In conclusion,this study identified 97 potential host factors interacting with PB1 protein by liquid chromatography-mass spectrometry.GO classification and KEGG analysis revealed that the molecular functions of these host factors were mainly involved in polyadenosine RNA binding,protein binding and ribosome structural component;Protein interaction network analysis found that these host factors were mainly involved in ribosome metabolic pathway,RNA transport pathway and spliceosome pathway.This study further explored the regulation mechanism of host factor YB1 on IAV replication,and briefly studied the effects of host factors such as PRMT5,FABP5,KCTD2,LRPPRC,SF1,WDR77 and YWHAB on virus proliferation.This study confirmed that YB1 and YWHAB can interact with PB1,and PRMT5 can interact with PB2 by coimmunoprecipitation assay.By silencing the expression of host factors by siRNA,this study found that host factors YB1,YWHAB,SF1,PRMT5 and WDR77 promoted the replication of H1N1 influenza virus.This study not only deepened the understanding of mechanism of the IAV replication,but also further provided potential targets for anti-IAV drugs.