The influenza B virus (IBV) causes seasonal influenza and has accounted for an increasing proportion of influenza outbreaks. IBV mainly causes human infections and has not been found to spread in poultry. The replication mechanism and the determinants of interspecies transmission of IBV are largely unknown. In this study, we found that the host ANP32 proteins are required for the function of the IBV polymerase. Human ANP32A/B strongly supports IBV replication, while ANP32E has a limited role. Unlike human ANP32A/B, chicken ANP32A has low support activity to IBV polymerase because of a unique 33-amino-acid insert, which, in contrast, exhibits species specific support to avian influenza A virus (IAV) replication. Chicken ANP32B and ANP32E have even lower activity compared with human ANP32B/E due to specific amino acid substitutions at sites 129-130. We further revealed that the sites 129-130 affect the binding ability of ANP32B/E to IBV polymerase, while the 33-amino-acid insert of chicken ANP32A reduces its binding stability and affinity. Taken together, the features of avian ANP32 proteins limited their abilities to support IBV polymerase, which could prevent efficient replication of IBV in chicken cells. Our results illustrate roles of ANP32 proteins in supporting IBV replication and may help to understand the ineffective replication of IBV in birds.

BackgroundInfluenza A virus (IAV) infection is a serious public health problem not only in South East Asia but also in European and African countries. Scientists are using network biology to dig deep into the essential host factors responsible for regulation of virus infections. Researchers can explore the virus invasion into the host cells by studying the virus-host relationship based on their protein-protein interaction network.MethodsIn this study, we present a comprehensive IAV-host protein-protein interaction network that is obtained based on the literature-curated protein interaction datasets and some important interaction databases. The network is constructed in Cytoscape and analyzed with its plugins including CytoHubba, CytoCluster, MCODE, ClusterViz and ClusterOne. In addition, Gene Ontology and KEGG enrichment analyses are performed on the highly IAV-associated human proteins. We also compare the current results with those from our previous study on Hepatitis C Virus (HCV)-host protein-protein interaction network in order to find out valuable information.ResultsWe found out 1027 interactions among 829 proteins of which 14 are viral proteins and 815 belong to human proteins. The viral protein NS1 has the highest number of associations with human proteins followed by NP, PB2 and so on. Among human proteins, LNX2, MEOX2, TFCP2, PRKRA and DVL2 have the most interactions with viral proteins. Based on KEGG pathway enrichment analysis of the highly IAV-associated human proteins, we found out that they are enriched in the KEGG pathway of basal cell carcinoma. Similarly, the result of KEGG analysis of the common host factors involved in IAV and HCV infections shows that these factors are enriched in the infection pathways of Hepatitis B Virus (HBV), Viral Carcinoma, measles and certain other viruses.ConclusionIt is concluded that the list of proteins we identified might be used as potential drug targets for the drug design against the infectious diseases caused by Influenza A Virus and other viruses.