分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.
分类: 生物学 >> 生物物理学 >> 生物力学与生物流变学 提交时间: 2016-05-12
摘要: The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbidity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-like strains) and HK14 (A/Hong Kong/5738/2014-like strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in mainland China, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an important role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.
分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-12
摘要: Replication and transcription of influenza virus genome mainly depend on its RNA-dependent RNA polymerase (RdRP), composed of the PA, PB1, and PB2 subunits. Although extensively studied, the underlying mechanism of the RdRP complex is still unclear. Here we report the biochemical characterization of influenza RdRP subcomplex comprising PA, PB1, and N terminus of PB2, which exist as dimer in solution and can assemble into a tetramer state, regulated by vRNA promoter. Using single-particle cryo-electron microscopy, we have reconstructed the RdRP tetramer complex at 4.3 angstrom, highlighting the assembly and interfaces between monomers within the tetrameric structure. The individual RdRP subcomplex contains all the characterized motifs and appears as a cage-like structure. High-throughput mutagenesis profiling revealed that residues involved in the oligomer state formation are critical for viral life cycle. Our results lay a solid base for understanding the mechanism of replication of influenza and other negative-stranded RNA viruses.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: Protein-protein interaction (PPI) networks serve as a powerful tool for unraveling protein functions, disease-gene and disease-disease associations. However, a direct strategy for integrating protein interaction, protein function and diseases is still absent. Moreover, the interrelated relationships among these three levels are poorly understood. Here we present a novel systematic method to integrate protein interaction, function, and disease networks. We first identified topological modules in human protein interaction data using the network topological algorithm (NeTA) we previously developed. The resulting modules were then associated with functional terms using Gene Ontology to obtain functional modules. Finally, disease modules were constructed by associating the modules with OMIM and GWAS. We found that most topological modules have cohesive structure, significant pathway annotations and good modularity. Most functional modules (70.6%) fully cover corresponding topological modules, and most disease modules (88.5%) are fully covered by the corresponding functional modules. Furthermore, we identified several protein modules of interest that we describe in detail, which demonstrate the power of our integrative approach. This approach allows us to link genes, and pathways with their corresponding disorders, which may ultimately help us to improve the prevention, diagnosis and treatment of disease.