Proteolytic activation of the hemagglutinin as a fusion protein has been known for. Pdf study of immunogenicity of recombinant proteins. Mumps virus is one of the main cause of respiratory illnesses in humans, especially children. The chemistry of antigenic variation in influenza a virus hemagglutinin. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replication. Mar 27, 2017 influenza a virus iav membrane proteins hemagglutinin ha and neuraminidase na are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. All but h17n10 and h18n11 subtypes, found to date in peruvian bats,14, circulate in wild aquatic birds, which is by far the largest of the known natural iav reservoirs, which also include humans, swine, horses, dogs, and seals. Jan 25, 2019 broadly neutralizing antibodies abs that bind the influenza virus hemagglutinin ha stem may enable universal influenza vaccination. Cn101983069b influenza hemagglutinin and neuraminidase. The hemagglutinin protein of influenza virus mediates virus attachment to a ciliated cell glycoconjugate terminating in sialic acid and causes fusion with an intracellular endosomal membrane at low ph. A glycoprotein is a protein that contains a short chain of sugar as part of its. Several potent and specific inhibitors of this enzyme have been developed, and two zanamivir and oseltamivir have been approved for human use.
Virology 214, 294300 1995 short communication hemagglutinin neuraminidase of human parainfluenza 3. The role of hemagglutinin and neuraminidase in influenza virus. In the current study, a simple method for producing reference. We concluded that cooperation of ha and na moves iav particles on a cell surface and enhances virus infection of host cells. The role of hemagglutinin and neuraminidase in influenza. View fulltext html download pdf track your manuscript. Pdf on jan 1, 2005, elspeth garman and others published the structure, function, and inhibition of influenza. Influenza a virus iav has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Influenza a virus iav membrane proteins hemagglutinin ha and neuraminidase na are determinants of virus infectivity, transmissibility, pathogenicity, host.
Jun 04, 20 a longheld dogma posits that strong presentation to the immune system of the dominant influenza virus glycoprotein antigens neuraminidase na and hemagglutinin ha is paramount for inducing protective immunity against influenza virus infection. Neuraminidase inhibition contributes to influenza a virus. Hemagglutinin and neuraminidase protrude from the outer surface of the influenza virus and neuraminidase is a constituent of the enveloping membrane that surrounds the viral contents. At high temperature, cells infected with this virus did not exhibit haemadsorption activity, but the addition of bacterial neuraminidase bna restored haemadsorption activity. Crystal structure of the multifunctional paramyxovirus hemagglutininneuraminidase. Influenza virus neuraminidase structure and functions. Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel h7n9 influenza virus using the baculovirus expression system. Coronavirus oc43 entered the human population relatively recently. These two glycoproteins both recognize the sialic acid and have complementary. The piv hemagglutininneuraminidase glycoprotein mediates attachment to sialic acidcontaining host cell receptors. Hemagglutininneuraminidase and fusion proteins of virulent. Influenza a viruses iavs occasionally cross the species barrier and adapt to novel host species.
Influenza virus haemagglutinin ha and neuraminidase na are. An analysis of the role of neuraminidase in the receptor. Development of neuraminidase subtypespecific reference. It initiates infection by binding to cell surface receptors and by inducing membrane fusion. The high variability of the influenza virus genome is reflected by a wide spectrum in host tropism, tissue specificity, and pathogenicity, ranging from local infection of the respiratory tract or the gut, as is the case with most mammalian strains and the apathogenic avian viruses, to systemic infection caused by fowl plague virus or other highly pathogenic avian strains. Here we use it to produce correctly folded and glycosylated versions of the influenza a virus surface glycoproteins the hemagglutinin ha and the neuraminidase. Pdf the structure, function, and inhibition of influenza virus. A method for determining avian influenza virus hemagglutinin. The envelope contains two major glycoproteins present as 8 to 14 nm spikelike projections. Neuraminidase sialidase enzymes are glycoside hydrolase enzymes that cleave cut the glycosidic linkages of neuraminic acids. Antiinfluenza drugs mimic the natural sialic acid substrate of the virus neuraminidase enzyme but utilize the much tighter binding of the drugs for. We have analyzed the mechanism by which the matrix m1 protein associates with cellular membranes during influenza a virus assembly. Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel h7n9.
Although most seasonal inactivated influenza vaccines iiv contain neuraminidase na, the extent and mechanisms of action of protective human naspecific humoral responses induced by vaccination are poorly resolved. Influenza a virus entry inhibitors targeting the hemagglutinin. Although the influenza a virus surface glycoprotein neuraminidase na has. Ha binds sa through its receptorbinding sites, while na is a receptordestroying enzyme by removing sas.
Seasonal influenza a and b viruses are important human pathogens responsible for significant morbidity and mortality worldwide. These two glycoproteins both recognize the sialic acid and have. Methods for grouping specific avian influenza virus aiv hemagglutinin ha and neuraminidase na subtype reversetranscription polymerase chain reaction rtpcr products into ha. Influenza virus is continually changing and every decade or so, a dangerous new strain appears and poses a threat to public health. The ha and neuraminidase na glycoproteins are the 2 major surface antigens of the influenza virus and facilitate infection, replication, and viral shedding. Fusion activation by a headless parainfluenza virus 5. These vaccines have long been evaluated based on the antibody response they elicit, particularly to the viral hemagglutinin ha 1, 2. Nov 29, 2019 vaccination and the use of neuraminidase inhibitors nais are currently the front lines of defense against seasonal influenza. Incorporation of m1 into vlps required ha expression, although when m1 was omitted from vlps, particles with morphologies similar to those of wildtype vlps or viruses were observed. Influenza virus hemagglutinin and neuraminidase, but not the. A novel neuraminidasedependent hemagglutinin cleavage.
Neuraminidase enzymes are a large family, found in a range of organisms. Influenza hemagglutinin ha or haemagglutinin p british english is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity. Influenza a virus hemagglutinin and neuraminidase act as novel. Revisiting the 1976 swine flu vaccine clinical trials. Influenza hemagglutinin and neuraminidase membrane.
Influenza virus andor hemagglutinin andor neuraminidase, detection hemagglutinin sample andor neuraminidase sample sequence, the utilization that can in diagnostic test, use nucleotide sequence of the present invention to detect in sample detect strain difference in influenza clinical isolates as being selected from the chemosynthesis of. Pdf avian influenza virus with hemagglutininneuraminidase. Due to the propensity of influenza virus for antigenic drift and shift and its tendency to elicit predominantly strainspecific antibodies, humanity remains susceptible to waves. Hemagglutininneuraminidase of human parainfluenza 3.
Hemagglutinin designated as ha and neuraminidase designated as na are glycoproteins. Our previous study suggested that the f and hn of virulent ndv synergistically induced significant syncytium formation accompanied with complete autophagic flux in df1 and a549 cells. Influenza hemagglutinin and neuraminidase membrane glycoproteins. Genome stability of pandemic influenza a h1n1 2009 based. Functional balance between neuraminidase and haemagglutinin in. The paramyxoviridae family of enveloped viruses enters cells through the concerted action of two viral glycoproteins. Nowadays, influenza virus is still a big threat to human. A novel neuraminidasedependent hemagglutinin cleavage mechanism enables the systemic spread of an h7n6 avian influenza virus. Functional balance between neuraminidase and haemagglutinin.
Pdf glycosylation of the hemagglutinin ha and neuraminidase na of the influenza provides crucial means for immune. Antigenic drift of hemagglutinin and neuraminidase in. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins. Influenza virus neuraminidase inhibitors the lancet. These subtypes are defined by their interaction with antibodies. Vaxarray for hemagglutinin and neuraminidase potency. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
Phylogenetic analysis of hemagglutinin and neuraminidase genes of highly pathogenic avian influenza h5n1 egyptian strains isolated from 2006 to 2008 indicates. Pdf we report the genome sequence of an avian influenza virus aiv subtype h8n8, isolated in russia. Interaction of the m1 protein with the viral hemagglutinin ha or neuraminidase na glycoprotein was extensively analyzed by using wildtype and transfectant influenza viruses as well as recombinant vaccinia viruses expressing the m1 protein, ha, or na. The envelope glycoproteins, hemagglutinin ha and neuraminidase na, mediate. Eighteen hemagglutinin and 11 neuraminidase subtypes are known to exist in nature. These subtypes are one of the causes of the continual effectiveness of influenza. Note that agglutination is one of three steps in the more complex process of coagulation. Jan 31, 2020 mumps virus is one of the main cause of respiratory illnesses in humans, especially children. Member viruses of the family paramyxoviridae are enveloped, 150 to 300 nm in diameter, ranging in shape from spherical to almost filamentous. Pdb entry 1qfu shows how one antibody attacks hemagglutinin, blocking it so that it cannot bind to cell surfaces. Neuraminidase hemagglutinin abstract practical methods to measure the potency of in.
Its neuraminidase domain has the cazy designation glycoside hydrolase family 83 gh83. Influenza a virions possess two surface glycoproteinsthe hemagglutinin ha and neuraminidase nawhich exert opposite functions. Yonsei university, 50 yonseiro, seodaemungu, seoul 03722, korea. Sep 10, 2009 neuraminidase na recognizes the same molecule as hemagglutinin, sialic acid of the cell membrane, but it performs its function in an opposite way, its role is to help the virus to leave the invaded cell. The activity of influenza vaccines and antivirals drugs such as the nais can be affected by mutations in the influenza hemagglutinin ha protein. Inhibition of neuraminidase by ganoderma triterpenoids and. Neuraminidase na inhibitors are the dominant antiviral drugs for treating influenza in the clinic. The structure includes hemagglutinin, shown in blue and orange, and three copies of a fab fragment of antibody fab fragments are one arm from the y shaped antibody. The hemagglutinin ha and neuraminidase na of influenza a virus possess antagonistic activities on interaction with sialic acid sa, which is the receptor for virus attachment. Initiation of virus infection involves multiple has binding to sialic acids on carbohydrate side chains of cellsurface glycoproteins and glycolipids 4, 6. Influenza hemagglutinin and neuraminidase variants download pdf info publication number cn104278014a. Hemagglutinin is a protein that binds tightly to the sugar portions of various cellsurface glycoproteins by recognizing and binding the sugar sialic acid, which is also called nacetyl neuraminic acid.
The two glycoproteins of the influenza virus membrane, hemagglutinin ha 3 and neuraminidase na, both recognize sialic acid 1 3. Among the viral surface glycoproteins, the hemagglutinin neuraminidase, muvhn, plays key roles in virus entry into host cells and infectivity, thus representing an ideal target for the design of novel inhibitors. Correlation of crossreactive hemagglutinin inhibition hai and neuraminidase inhibition nai antibodies with protection in recipient mice against the 2009 h1n1 pandemic viruses after passive transfer of the 1976 swine flu vaccination human serum samples. Study of immunogenicity of recombinant proteins based on hemagglutinin and neuraminidase conservative epitopes of influenza a virus. Hemagglutinin ha and neuraminidase na are the two viral surface proteins, which play important roles in the life cycle of influenza virus. The hemagglutinin ha is a prime determinant of the pathogenicity of influenza a viruses. The receptorbinding protein, hemagglutininneuraminidase hn, h, or g, binds its cellular receptor and activates the fusion protein, f, which, through an extensive refolding event, brings viral and cellular membranes together, mediating viruscell fusion. The molecular characterizations of surface proteins hemagglutinin and. Deliberate reduction of hemagglutinin and neuraminidase. Influenza a virions possess two surface glycoproteinsthe hemagglutinin. View enhanced pdf access article on wiley online library html view download pdf for offline viewing.
Jul 14, 2016 seasonal influenza a and b viruses are important human pathogens responsible for significant morbidity and mortality worldwide. Functional balance between neuraminidase and haemagglutinin in influenza viruses. Competitive cooperation of hemagglutinin and neuraminidase. Antibodies to influenza b virus could also be measured by the srh technique. The function of ha during virus entry has been extensively investigated, however, examination of na has long. The piv hemagglutininneuraminidase glycoprotein mediates attachment to sialic acid. The bestknown neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread of influenza infection. Such measures require diagnostic tests to detect and characterize the different subtypes of influenza virus. And the abovementioned any fragment that comprises hemagglutinin or neuraminidase peptide sequence, or hemagglutinin or neuraminidase polypeptide fragment, preferably produce the fragment of the antibody of specific binding fulllength polypeptide of the present invention. Structural basis for glycanreceptor binding by mumps virus. Jul 29, 2015 longterm observation of hemagglutinin and neuraminidase inhibition antibody titers after influenza challenge the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Betacoronavirus adaptation to humans involved progressive.
Structure of influenza hemagglutinin in complex with an. Therefore, ha is responsible for binding influenza virus to sialic acid on the surface of target cells, such as cells in the upper respiratory tract or erythrocytes, following which event the virus is internalised. In addition, influenza a zoonotic viruses are a constant pandemic threat. Hemagglutinin ha, the envelope glycoprotein of iav, plays a critical role in viral binding, fusion and entry. The influenza b virus mutant ts7 has a temperaturesensitive mutation in the na protein. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of iav infection. Broadly neutralizing antibodies abs that bind the influenza virus hemagglutinin ha stem may enable universal influenza vaccination. Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. Na subtypes when egg incubation is technically not feasible were evaluated. However, the roles of the fusion f and hemagglutinin neuraminidase hn glycoproteins of newcastle disease virus ndv in mitochondrial have yet to be studied. This resulted in a clear separation of hemagglutinin and neuraminidase activities and. Neuraminidase na recognizes the same molecule as hemagglutinin, sialic acid of the cell membrane, but it performs its function in an opposite way, its role is to help the virus to leave the invaded cell.
Role of the neuraminidase in the viral life cycle kety huberman, richard w. Influenza a virus hemagglutinin mutations associated with use. 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. However, the roles of the fusion f and hemagglutininneuraminidase hn glycoproteins of newcastle disease virus ndv in mitochondrial.
Unlike amantadine and rimantadine that target the m2 protein of influenza a viruses, these drugs inhibit replication of both. Hemagglutinin ha and neuraminidase na hemagglutinin designated as ha and neuraminidase designated as na are glycoproteins. Vaccination and the use of neuraminidase inhibitors nais are currently the front lines of defense against seasonal influenza. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of apr834 h1n1 in which expression of na and ha.
Neuramidase is needed to remove the acid from the cell and to allow the recently synthesized virus to sprout and invade the next cell. Proteolytic activation of the hemagglutinin as a fusion protein has been known for a long. A longheld dogma posits that strong presentation to the immune system of the dominant influenza virus glycoprotein antigens neuraminidase na and hemagglutinin ha is paramount for inducing protective immunity against influenza virus infection. Peluso, and anne moscona,1 departments of pediatrics and cell biologyanatomy and microbiology, mount sinai school of medicine, 1 gustave l. Hemagglutinin neuraminidase refers to a single viral protein that has both hemagglutinin and endo neuraminidase ec 3. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of apr834 h1n1 in which expression of na. Among the viral surface glycoproteins, the hemagglutinin neuraminidase, muvhn, plays key roles in. Hemagglutininneuraminidase an overview sciencedirect topics. The structure of ha in complex with a known inhibitor of membrane fusion and virus infectivity, tert butyl hydroquinone tbhq, shows that the inhibitor binds in a hydrophobic. Pdf glycosylation of hemagglutinin and neuraminidase of. Sep 10, 2010 the two glycoproteins of the influenza virus membrane, hemagglutinin ha 3 and neuraminidase na, both recognize sialic acid 1, 3. Evaluation of the single radial hemolysis test for.
Current influenza vaccines and antiinfluenza drugs work. Cn104278014a influenza hemagglutinin and neuraminidase. Vaxarray for hemagglutinin and neuraminidase potency testing. Antigenic drift of the hemagglutinin ha and neuraminidase na proteins of influenza virus cause decrease in vaccine efficacy. He then found that when the agglutinated cells were warmed to 37 c they dispersed as the. These viruses present two major surface glycoproteins. Longterm observation of hemagglutinin and neuraminidase. Numerous ha substitutions have been identified in nonclinical nai resistanceselection experiments as well as in clinical. Initiation of virus infection involves multiple has binding to sialic acids on carbohydrate side chains of cellsurface glycoproteins and glycolipids 4 6. Persistence of antibodies to influenza hemagglutinin and.
Hemagglutinin is a class i fusion protein, having multifunctional activity as both an attachment factor and membrane fusion protein. Influenza a virus hemagglutinin and neuraminidase act as. The molecular characterizations of surface proteins hemagglutinin. Neuraminidase activity and specificity of influenza a. Antibodies to the h3 hemagglutinin of influenza a virus could be specifically measured by single radial hemolysis srh when test antigens were recombinant viruses containing the relevant h3 hemagglutinin antigen and irrelevant neq1 neuraminidase of aequineprague156 virus. The influenza virus major surface glycoproteins, hemagglutinin ha, and. Here, we show that antistem abs sterically inhibit viral neuraminidase na activity against large substrates, with activity inversely proportional to the length of the fibrous na stalk that supports the enzymatic domain. Broad and protective influenza b virus neuraminidase. We analysed the role of neuraminidase na on haemadsorption by the haemagglutinin ha protein of influenza b virus. The influenza surface glycoprotein hemagglutinin ha is a potential target for antiviral drugs because of its key roles in the initial stages of infection. Hemagglutininneuraminidase an overview sciencedirect. Webster rg, bean wj, gorman ot, chambers tm, kawaoka y. The chemistry of antigenic variation in influenza a virus. Influenza a virus hemagglutinin mutations associated with use of.
Influenzahemagglutininand neuraminidasemembrane glycoproteins. The medicinal potential of influenza virus surface. Consequently, virionassociated receptordestroying activity toward clustered sialoglycanbased receptor determinants was reduced. The specificity of virus attachment to target cells is mediated by hemagglutinin, which acquires characteristic changes in its receptorbinding site to switch its host from avian species to humans. Expression of functional recombinant hemagglutinin and. Neuraminidase and hemagglutinin matching patterns of a highly.
249 14 312 1335 995 298 1087 309 910 835 862 869 383 1276 470 1 525 259 189 1073 1562 1460 394 51 255 90 992 1085 1452 1190 543