Xuyong li, jianzhong shi, jing guo, guohua deng, qianyi zhang, jinliang wang, xijun he, kaicheng wang, jiming chen, yuanyuan li. Structural basis for receptor specificity of influenza b. How bat influenza viruses infect cells has been unclear. We isolated highly pathogenic avian influenza ah5n6 virus clade 2. The discovery that they bind to a cell receptor that is present in many different species raises concerns about their potential risk to humans. Influenza risk assessment tool irat virus report prepared by the cdc influenza division. This requires readjustment of the functional balance of the sialic acid receptor binding hemagglutinin ha and the receptor destroying neuraminidase na to the sialoglycan receptor repertoire of the new host. However, details of the humanadaptive change in the h5n1 virus remain unknown.
Pdf on feb 1, 2015, yiwu yan and others published angiotensin ii receptor blocker as a novel therapy in acute lung injury induced by avian influenza a h5n1 virus infection in mouse find, read. This requires readjustment of the functional balance of the sialic acid receptorbinding hemagglutinin ha and the receptordestroying neuraminidase na to the sialoglycanreceptor repertoire of the new host. Cellular receptors capable of reacting with influenza viruses such as those on erythrocytes, and the cells lining the respiratory tract of the mouse or. Glycan receptor binding determinants of influenza a virus. The receptor preference of influenza viruses request pdf. Genetics, receptor binding property, and transmissibility in mammals of naturally isolated h9n2 avian influenza viruses. Binding of influenza virus hemagglutinin to analogs of its.
Entry of the virus is mediated by functions of the ha. Genetic characterization of avian influenza ah5n6 virus. Mar 12, 2020 the study shows that immunization with adeno. Receptor for bat influenza virus uncovers potential risk to.
The interplay between the host receptor and influenza virus. Influenza virus receptors in the human airway nature. Structure and receptor binding of the hemagglutinin from a. Influenza, commonly known as the flu, is an infectious disease caused by an influenza virus. The approaches presented in this thesis to systematically investigate molecular interactions between ha and glycan receptors that impinge on quantitative haglycan receptor binding affinity offer a new angle towards studying determinants of human receptor binding specificity and affinity of influenza a virus has. Here we report the structures of influenza b virus ha in complex with human and avian. At high temperature, cells infected with this virus did not exhibit haemadsorption activity, but the addition of bacterial neuraminidase bna restored haemadsorption activity. Cell receptors for influenza a viruses and the innate.
Receptor binding by an h7n9 influenza virus from humans nature. Timely identification of pandemic influenza threats depends on monitoring for highly pathogenic avian influenza viruses. There is still a good possibility that statins might contribute to improved survival in human influenza because, among other things, they down regulate proinflammatory cytokines. These symptoms typically begin two days after exposure to the virus and most last.
H3n2 human influenza isolates lost binding to chicken red cells in the 1990s but viruses isolated since 2003 have reacquired the ability to agglutinate chicken erythrocytes. This site is a key determinant of pathogenicity in avian species and describes the switch between low pathogenicity and highly pathogenic avian influenza viruses. Receptor binding and membrane fusion in virus entry. Recently, we demonstrated, using an in vitro approach, that the pattern recognition tolllike receptor tlr3 plays a key role in the immune response of lung epithelial cells to iav. Viropexis, the mechanism of influenza virus infection nature. Association of increased receptor binding avidity of. An analysis of the role of neuraminidase in the receptor. The cell surface receptor used by an influenza virus to infect that cell is an nacetyl neuraminic acid nana residue terminally linked by an alpha2,3 or alpha2,6 bond to a carbohydrate moiety of a glycoprotein or glycolipid. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in ha immediately adjacent to the receptor binding site. The overall interaction strength can be modulated by changing the number of engaged receptors. Receptor binding specificity of recent human h3n2 influenza. Steinhauer 1, 1 department microbiology and immunology, emory university school of medicine, atlanta, ga 30307, usa.
A change in viral hemagglutinin ha receptor binding specificity from. Aug 01, 2002 influenza virusinduced neutrophil dysfunction has been studied in a chinchilla model and contributes to the development of acute purulent otitis media from pneumococcus. Jul 20, 20 sialic acid was the first virus receptor identified. Therefore, the receptor specificity of influenza viruses is important not only for the host tropism, but also for tissue tropism in humans, since it determines the airway region and cell types that support active viral replication, what might contribute to the severity of the disease observed in humans infected. Conserved t cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope katherine kedzierska, stephen j.
Barclay, lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity in vivo, journal of general virology, 92, 8, 1822, 2011. This encouraged scientists to elucidate the glycome of the respiratory. Treating the host response to emerging virus diseases. The interplay between the host receptor and influenza virus hemagglutinin and neuraminidase article pdf available in international journal of molecular sciences 187. Human influenza viruses are known to bind to sialic acid linked. Attachment first step surface protein on virus attaches to specific receptors on cell surfacemay be specialized proteins with limited tissue distribution or more widely distributedvirus specific receptor is necessary but not sufficient for viruses to infect cells and complete replicative cycle. Evaluation of influenza a virus receptors request pdf. Pdf the interplay between the host receptor and influenza. Protection correlated with induction of antibodies targeting the head and stalk regions of the viral protein ha, and activating fc. In contrast, has from human influenza virus strains show enhanced binding to. Mobilitybased quantification of multivalent virusreceptor.
Interestingly, the scope of s1p receptor therapy reported here is likely to extend beyond influenza virus infection and could prove useful for the treatment of multiple maladies like other viral infections and autoimmune diseases where the hosts inflammatory response is a major component in the disease process. Role of receptor binding specificity in influenza a virus. Most avian influenza viruses preferentially bind to sialic acid receptors that contain nacetylneuraminic acid 2,3galactose. The cell surface receptor used by an influenza virus to infect that cell is an nacetyl neuraminic acid nana residue terminally linked by an alpha2,3 or alpha2,6 bond to a carbohydrate moiety of. Influenza a viruses iavs occasionally cross the species barrier and adapt to novel host species. The nachr was the first rabies virus receptor identified and this receptor is felt to be important for the spread of the virus from the neuromuscular junction at peripheral sites in order to gain access to the cns along peripheral nerves lentz et al. Jun 20, 20 an examination of the receptorbinding properties of the h7n9 virus, which has recently emerged in china, shows that the virus has acquired the ability to bind the human. Influenza type b virus almost exclusively infects humans and contributes to the annual flu sickness. Jul 11, 2007 the receptor binding preference of h5n1 viruses can be altered by only a few amino acid substitutions in the hemagglutinin ha protein. Mar 19, 2004 receptor binding, the initial event in virus infection, is a major determinant of virus transmissibilitythat, for influenza viruses, is mediated by the hemagglutinin ha membrane glycoprotein.
In view of these data and the fact that the functional. Characterization of h5n1 influenza virus variants with. Influenza d virus is a species in the virus genus influenzavirus d, in the family orthomyxoviridae, that causes influenza influenza d viruses are known to infect pigs and cattle. The receptor specificity of influenza virus ha correlates with the ability to agglutinate rbc from different animal species. The discovery that they bind to a cell receptor that is present in many different species raises concerns about their potential risk. Structural basis for receptor specificity of influenza b virus hemagglutinin qinghua wang, xia tian, xiaorui chen, and jianpeng ma department of biochemistry and molecular biology, baylor college of medicine, one baylor plaza, bcm125, houston, tx 77030.
Sa alpha 2,6 and sa alpha 2,3 linked sialic acid molecules on epithelial cell membrane served as receptors for. Antigenspecific bcell receptor sensitizes b cells to. Hirst and mcclelland and hare discovered that influenza virus is able to hemagglutinate and that adsorbed virus is eluted from erythrocytes on incubation at 37c, indicating an enzymatic destruction of a receptor substance on the cells 1, 2. The current common belief is that for airborne transmission between humans or ferrets, influenza viruses require human over avian receptor binding preference. Cos cells transfected with ha cdnas of bkanagawa73 or blee40 virus showed. Receptor for bat influenza virus uncovers potential risk. The interplay between the host receptor and influenza. An avian influenza h5n1 virus that binds to a humantype receptor. Human infections with novel influenza a viruses that originate in animals are rare and the overall risk of such. Laboratory procedures serological detection of avian.
Influenza a virus hemagglutininneuraminidasereceptor. Apr 16, 2014 binding assays such as glycan arrays, which allow the investigation of hundreds of different sialylated glycan structures, have demonstrated that influenza virus receptor specificity also involves structural modifications of the sa and overall glycan gambaryan et al, 2005. The molecular basis of antigenic drift was determined for the hemagglutinin ha of human influenza ah3n2 virus. Influenza virus h10n8 is the most recent example of an avian influenza virus that has infected and killed humans. The structure and receptor binding properties of the 1918. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 at1r blockers, such as losartan, as therapeutics for. The virus has high homology to human h5n6 influenza strains isolated from southeast china. Viruses, such as influenza a, typically bind to the plasma membrane of their host by engaging multiple membrane receptors in parallel, thereby forming socalled multivalent interactions that are created by the collective action of multiple weak ligandreceptor bonds. Detrimental contribution of the tolllike receptor tlr3 to. Pdf angiotensin ii receptor blocker as a novel therapy.
However, the outcome of interactions between a flu hemagglutinin haspecific b cell via its receptor bcr and virus is unclear. Influenza a virus specific b lymphocytes and the antibodies they produce protect against infection 1. Unfortunately, lectin staining provides little information on the differences in overall glycan structures, including the number of antennas, fucosylation, and the presence of n. Steven gamblin and colleagues investigate the structure and receptor. Statins reduce influenza virus replication in vitro, but for several reasons, studies of statin treatment of influenza virusinfected mice have been inconclusive. Novel techniques have revealed mechanistic details of this hanareceptor balance. Conserved t cell receptor usage in primary and recall. The influenza b virus mutant ts7 has a temperaturesensitive mutation in the na protein. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibilitythat, for influenza viruses, is mediated by the hemagglutinin ha membrane glycoprotein. Receptor binding specificity of ha, the major surface glycoprotein of influenza virus, primarily determines the host ranges that the virus can infect. Indeed, new influenza virus strains emerge every year, requiring new immunizations. Influenza virus ha requires activation by host proteases at a conserved cleavage site between the ha1 and ha2 subunits. Hemagglutinin ha is the receptor binding and membrane fusion glycoprotein of influenza virus and the target for infectivityneutralizing antibodies. Thankfully there have been no reports of humantohuman transmission of the h5n1 avian influenza virus.
The hemagglutinin ha and neuraminidase na glycoproteins of influenza a virus are responsible for the surface interactions of the virion with the host. Request pdf evaluation of influenza a virus receptors sialic acid has long been considered the sole cellular receptor for influenza viruses, but it has been demonstrated that influenza can. The structures of three conformations of the ectodomain of the 1968 hong kong influenza virus ha have been determined by xray crystallography. Substitutions near the receptor binding site determine major. Avian and human flu viruses seem to target different regions of a patients respiratory tract. Receptor specificity of the influenza virus hemagglutinin modulates sensitivity to soluble collectins of the innate immune system and virulence in mice. Asian lineage low pathogenic avian influenza ah7n9 virus. Mutations that change the receptor binding preference from the avian to the human type could potentially enable the virus to transmit efficiently in the human population and cause a catastrophic pandemic. Lethal synergism between influenza virus and streptococcus. Influenza virus infection has deleterious effects on macrophages, depressing chemotaxis and suppressing phagocytosis. We have determined the crystal structures of the ha from the 1918 virus and two closelyrelated has in complex with receptor analogs. Influenza a virus iav is the etiological agent of a highly contagious acute respiratory disease that causes epidemics and considerable mortality annually.
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