Three-dimensional structure of a complex of antibody with influenza virus neuraminidase

The structure of a complex between influenza virus neuraminidase and an antibody displays features inconsistent with the inflexible 'lock and key' model of antigen-antibody binding. The structure of the antigen changes on binding, and that of the antibody may also change; the interaction therefore has some of the character of a handshake.     

Antigenic epitope peptides of influenza H3N2 virus neuraminidase gene based on experiments

The neuraminidase (NA) in viral surface is one of the main subtype-specific antigen of influenza type A viruses.Neuraminidase is an enzyme to break the bonds between hemagglutinin (HA) and sialic acid to release newly formed viruses from infected cells.In this study,the H3N2 subtype virus NA genes were sequenced and NA proteins were screened for B-cell epitopes and assessed based on immunoinformatics.Based on this results,four peptides DR6,EY7,VG8 and RE8 (covering amino acid residues 151-156,368-374,398-405 and 428-435,respectively) of the NA protein were synthesized artificially.These peptides were used to immunize New Zealand rabbits subcutaneously to raise antisera.Experimental results showed that these four peptides were capable of eliciting antibodies against H3N2 viruses in a specific and sensitive feature,detected in vitro by enzyme-linked immunosorbent assay.Moreover,hemadsorption anti-releasing effects took place in three three-antisera-mixtures at a dilution of 1:40.Alignment using NA gene database showed that amino acid residues in these four epitope peptides were substituted at specific sites in all the NAs sequenced in this study.It was suggested that these NA epitope peptides might be used in combination with HA proteins as vaccine antigens.     

TritonX-100裂解流感病毒的研究

 在流感病毒高浓度条件下,寻找TritonX-100裂解流感病毒的适宜条件.在不同条件下用TritonX-100裂解WHO推荐用2007～2008年度流感病毒疫苗毒株制备的3个亚型的流感病毒,用电镜观察裂解程度,通过蔗糖密度梯度离心纯化抗原后免疫动物,以检测疫苗的免疫效果.结果表明当流感病毒的血凝效价是1:16382,裂解时间为24h时,TritonX-100在质量分数为1%可以完全地裂解B型,质量分数达到2%才可以完全裂解流感病毒H1N1和H3N2,这说明TritonX-100对A,B亚型毒株的裂解效果不同.由于每年都要更换毒株工人生产新的流感疫苗,因此应该对使用TritonX-100的裂解不同亚型的流感病毒条件进行研究,以保证裂解疫苗的质量.     

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.     

Special features of the 2009 pandemic swine-origin influenza A H1N1 hemagglutinin and neuraminidase

Since the 2009 pandemic H1N1 swine-origin influenza A virus (09 S-OIV) has reminded the world about the global threat of the ever changing influenza virus,many questions regarding the detailed re-assortment of influenza viruses yet remain unanswered.Influenza A virus is the causative agent of the pandemic flu and contains 2 major antigenic glycoproteins on its surface:(i) hemagglutinin (HA);and (ii) neuraminidase (NA).The structures of the 09 S-OIV HA and NA proteins (09H1 and 09N1) have recently been resolved in our laboratory and provide some clues as to why the 09 S-OIV re-assortment virus is highly infectious with severe consequences in humans.For example,the 09H1 is highly similar to the HA of the 1918 influenza A pandemic virus in overall structure and especially in regards to its 5 defined antibody binding epitopes.For 09N1,its most distinctive feature is the lack of a 150-loop active site cavity,which was previously predicted to be present in all N1 NAs,and we hypothesize that the 150-loop may play a important role in the substrate specificity (α2,3 or α2,6 linked sialic acid receptors) and enzymatic mechanism of influenza NA.Combination of the HA and NA with special characteristics for the 09 S-OIV might contribute to its high increased transmissibility in humans.     

Characterization of the 1918 influenza virus polymerase genes

The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors, thereby having a role in host specificity. The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian sequences, the nucleotide sequences of the 1918 polymerase genes have more synonymous differences than expected, suggesting evolutionary distance from known avian strains. Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus, and propose that the 1918 virus was not a reassortant virus (like those of the 1957 and 1968 pandemics), but more likely an entirely avian-like virus that adapted to humans. These data support prior phylogenetic studies suggesting that the 1918 virus was derived from an avian source. A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.     

铜氧化物高温超导体的晶体结构和物理性能研究

阐述了铜氧化物高温超导体的晶体结构 ,指出导电区、蓄电区的划分和电子相图是铜氧化物高温超导体重要的共性特征 .介绍了分块模型及其在研究晶体结合能、弹性模量中的应用 ,对铜氧化物高温超导体结构和性能之间的关系作了探讨 .最后对当前高温超导体研究的几个热点问题及其应用前景予以简介 .