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. Initiation of virus infection involves multiple has binding to sialic acids on carbohydrate side chains of cellsurface glycoproteins and glycolipids 4 6. Recall that the surface of the influenza virion is covered with spikes of hemagglutinin and neuraminidase. 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. Such measures require diagnostic tests to detect and characterize the different subtypes of influenza virus. Crystal structure of the multifunctional paramyxovirus hemagglutininneuraminidase. 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. Hemagglutinin ha and neuraminidase na hemagglutinin designated as ha and neuraminidase designated as na are glycoproteins. Neuraminidase na inhibitors are the dominant antiviral drugs for treating influenza in the clinic. Longterm observation of hemagglutinin and neuraminidase. Consequently, virionassociated receptordestroying activity toward clustered sialoglycanbased receptor determinants was reduced.
Proteolytic activation of the hemagglutinin as a fusion protein has been known for a long. Pdb entry 1qfu shows how one antibody attacks hemagglutinin, blocking it so that it cannot bind to cell surfaces. The molecular characterizations of surface proteins hemagglutinin. Antibodies to influenza b virus could also be measured by the srh technique. 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. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replication. Antigenic drift of the hemagglutinin ha and neuraminidase na proteins of influenza virus cause decrease in vaccine efficacy. Member viruses of the family paramyxoviridae are enveloped, 150 to 300 nm in diameter, ranging in shape from spherical to almost filamentous. The bestknown neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread of influenza infection. The activity of influenza vaccines and antivirals drugs such as the nais can be affected by mutations in the influenza hemagglutinin ha protein. Influenza hemagglutinin and neuraminidase variants download pdf info publication number cn104278014a. Several potent and specific inhibitors of this enzyme have been developed, and two zanamivir and oseltamivir have been approved for human use.
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. Influenza a virus iav membrane proteins hemagglutinin ha and neuraminidase na are determinants of virus infectivity, transmissibility, pathogenicity, host. The paramyxoviridae family of enveloped viruses enters cells through the concerted action of two viral glycoproteins. Hemagglutinin ha, the envelope glycoprotein of iav, plays a critical role in viral binding, fusion and entry. Jan 31, 2020 mumps virus is one of the main cause of respiratory illnesses in humans, especially children. The role of hemagglutinin and neuraminidase in influenza.
Deliberate reduction of hemagglutinin and neuraminidase. These two glycoproteins both recognize the sialic acid and have complementary. Vaxarray for hemagglutinin and neuraminidase potency. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins. Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. 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. Functional balance between neuraminidase and haemagglutinin in influenza viruses. Cn104278014a influenza hemagglutinin and neuraminidase. Eighteen hemagglutinin and 11 neuraminidase subtypes are known to exist in nature. Hemagglutinin ha and neuraminidase na are the two viral surface proteins, which play important roles in the life cycle of influenza 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. Influenza a viruses iavs occasionally cross the species barrier and adapt to novel host species.
Jan 25, 2019 broadly neutralizing antibodies abs that bind the influenza virus hemagglutinin ha stem may enable universal influenza vaccination. We analysed the role of neuraminidase na on haemadsorption by the haemagglutinin ha protein of influenza b virus. Here we use it to produce correctly folded and glycosylated versions of the influenza a virus surface glycoproteins the hemagglutinin ha and the neuraminidase. 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. Genome stability of pandemic influenza a h1n1 2009 based. The ha and neuraminidase na glycoproteins are the 2 major surface antigens of the influenza virus and facilitate infection, replication, and viral shedding. Outbreaks of avian influenza a virus infection, particularly the h5n1 strains that have affected birds and some humans for the past 15 years, have highlighted the need for increased surveillance and disease control. Influenza a virus iav has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Phylogenetic analysis of hemagglutinin and neuraminidase genes of highly pathogenic avian influenza h5n1 egyptian strains isolated from 2006 to 2008 indicates.
A method for determining avian influenza virus hemagglutinin. Structural basis for glycanreceptor binding by mumps virus. 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. Pdf glycosylation of the hemagglutinin ha and neuraminidase na of the influenza provides crucial means for immune. Influenza virus neuraminidase inhibitors the lancet. Pdf we report the genome sequence of an avian influenza virus aiv subtype h8n8, isolated in russia. 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. Coronavirus oc43 entered the human population relatively recently. Its neuraminidase domain has the cazy designation glycoside hydrolase family 83 gh83. The two glycoproteins of the influenza virus membrane, hemagglutinin ha 3 and neuraminidase na, both recognize sialic acid 1 3. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of apr834 h1n1 in which expression of na.
Na subtypes when egg incubation is technically not feasible were evaluated. In 2009, there was an outbreak of a new strain of h1n1 flu, more commonly known as swine flu. Betacoronavirus adaptation to humans involved progressive. Influenza a virus hemagglutinin and neuraminidase act as novel. Hemagglutininneuraminidase of human parainfluenza 3. These subtypes are defined by their interaction with antibodies. Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel h7n9.
Influenza a virus hemagglutinin and neuraminidase act as. Persistence of antibodies to influenza hemagglutinin and. Competitive cooperation of hemagglutinin and neuraminidase. Influenza hemagglutinin and neuraminidase membrane glycoproteins. Revisiting the 1976 swine flu vaccine clinical trials. Influenza hemagglutinin and neuraminidase membrane. Influenza a virus hemagglutinin mutations associated with use. A novel neuraminidasedependent hemagglutinin cleavage mechanism enables the systemic spread of an h7n6 avian influenza virus. Note that agglutination is one of three steps in the more complex process of coagulation. The influenza b virus mutant ts7 has a temperaturesensitive mutation in the na protein. Hemagglutininneuraminidase an overview sciencedirect.
These approaches were adopted for use as post hoc methods after melt curve analysis. The influenza surface glycoprotein hemagglutinin ha is a potential target for antiviral drugs because of its key roles in the initial stages of infection. Yonsei university, 50 yonseiro, seodaemungu, seoul 03722, korea. Neuraminidase enzymes are a large family, found in a range of organisms. Influenza virus hemagglutinin and neuraminidase, but not the. Functional balance between neuraminidase and haemagglutinin in.
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. Nov 06, 20 the baculovirus expression system is a powerful tool for expression of recombinant proteins. 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. Hemagglutinin is a class i fusion protein, having multifunctional activity as both an attachment factor and membrane fusion protein. Influenza virus is continually changing and every decade or so, a dangerous new strain appears and poses a threat to public health. Peluso, and anne moscona,1 departments of pediatrics and cell biologyanatomy and microbiology, mount sinai school of medicine, 1 gustave l. Learn vocabulary, terms, and more with flashcards, games, and other study tools. The medicinal potential of influenza virus surface.
Influenza a virus hemagglutinin mutations associated with use of. The chemistry of antigenic variation in influenza a virus. Vaxarray for hemagglutinin and neuraminidase potency testing. Study of immunogenicity of recombinant proteins based on hemagglutinin and neuraminidase conservative epitopes of influenza a virus. Hemagglutininneuraminidase an overview sciencedirect topics. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of apr834 h1n1 in which expression of na and ha. Nowadays, influenza virus is still a big threat to human. Influenza a virus hemagglutininneuraminidasereceptor. We have analyzed the mechanism by which the matrix m1 protein associates with cellular membranes during influenza a virus assembly.
Cn101983069b influenza hemagglutinin and neuraminidase. Evaluation of the single radial hemolysis test for. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of iav infection. Methods for grouping specific avian influenza virus aiv hemagglutinin ha and neuraminidase na subtype reversetranscription polymerase chain reaction rtpcr products into ha. Neuraminidase sialidase enzymes are glycoside hydrolase enzymes that cleave cut the glycosidic linkages of neuraminic acids.
Functional balance between neuraminidase and haemagglutinin. Webster rg, bean wj, gorman ot, chambers tm, kawaoka y. A novel neuraminidasedependent hemagglutinin cleavage. Current influenza vaccines and antiinfluenza drugs work. Ha binds sa through its receptorbinding sites, while na is a receptordestroying enzyme by removing sas. However, the roles of the fusion f and hemagglutininneuraminidase hn glycoproteins of newcastle disease virus ndv in mitochondrial. Influenza a virions possess two surface glycoproteinsthe hemagglutinin ha and neuraminidase nawhich exert opposite functions. Nov 29, 2019 vaccination and the use of neuraminidase inhibitors nais are currently the front lines of defense against seasonal influenza. 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. Jul 14, 2016 seasonal influenza a and b viruses are important human pathogens responsible for significant morbidity and mortality worldwide. Pdf avian influenza virus with hemagglutininneuraminidase. Broadly neutralizing antibodies abs that bind the influenza virus hemagglutinin ha stem may enable universal influenza vaccination. Neuraminidase and hemagglutinin matching patterns of a highly. 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.
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. Fusion activation by a headless parainfluenza virus 5. Hemagglutininneuraminidase and fusion proteins of virulent. 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. The piv hemagglutininneuraminidase glycoprotein mediates attachment to sialic acidcontaining host cell receptors. 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. Neuraminidase activity and specificity of influenza a. The envelope contains two major glycoproteins present as 8 to 14 nm spikelike projections. Hemagglutinin neuraminidase refers to a single viral protein that has both hemagglutinin and endo neuraminidase ec 3. Structure of influenza hemagglutinin in complex with an. 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. The function of ha during virus entry has been extensively investigated, however, examination of na has long. Novel techniques have revealed mechanistic details of this hanareceptor balance.
Influenza a virions possess two surface glycoproteinsthe hemagglutinin. Influenza virus neuraminidase structure and functions. These subtypes are one of the causes of the continual effectiveness of influenza. Development of neuraminidase subtypespecific reference. At high temperature, cells infected with this virus did not exhibit haemadsorption activity, but the addition of bacterial neuraminidase bna restored haemadsorption activity. 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. 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. However, the roles of the fusion f and hemagglutinin neuraminidase hn glycoproteins of newcastle disease virus ndv in mitochondrial have yet to be studied. Neuramidase is needed to remove the acid from the cell and to allow the recently synthesized virus to sprout and invade the next cell. Unlike amantadine and rimantadine that target the m2 protein of influenza a viruses, these drugs inhibit replication of both. Additionally, hemagglutinin ha, when treated with exogenous neuraminidase na or coexpressed with viral na, could be released from cells independently of m1. Among the viral surface glycoproteins, the hemagglutinin neuraminidase, muvhn, plays key roles in. Neuraminidase inhibition contributes to influenza a virus. Antiinfluenza drugs mimic the natural sialic acid substrate of the virus neuraminidase enzyme but utilize the much tighter binding of the drugs for.
As with hemagglutinin, neuraminidase comes in a variety of subtypes named n1n9. 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. The piv hemagglutininneuraminidase glycoprotein mediates attachment to sialic acid. 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. We concluded that cooperation of ha and na moves iav particles on a cell surface and enhances virus infection of host cells. Pdf on jan 1, 2005, elspeth garman and others published the structure, function, and inhibition of influenza. In human h3 ha, for example, hydrogen bonds are formed between the carboxylate group of sia1 and ser6 and the. Pdf glycosylation of hemagglutinin and neuraminidase of. The envelope glycoproteins, hemagglutinin ha and neuraminidase na, mediate. He then found that when the agglutinated cells were warmed to 37 c they dispersed as the. Influenza a virus entry inhibitors targeting the hemagglutinin. Role of the neuraminidase in the viral life cycle kety huberman, richard w. The role of hemagglutinin and neuraminidase in influenza virus.
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. 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. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. In the current study, a simple method for producing reference. The chemistry of antigenic variation in influenza a virus hemagglutinin. Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel h7n9 influenza virus using the baculovirus expression system. Initiation of virus infection involves multiple has binding to sialic acids on carbohydrate side chains of cellsurface glycoproteins and glycolipids 4, 6. 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. 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. Although the influenza a virus surface glycoprotein neuraminidase na has. These two glycoproteins both recognize the sialic acid and have.
In addition, influenza a zoonotic viruses are a constant pandemic threat. A glycoprotein is a protein that contains a short chain of sugar as part of its. These viruses present two major surface glycoproteins. Virology 214, 294300 1995 short communication hemagglutinin neuraminidase of human parainfluenza 3. It initiates infection by binding to cell surface receptors and by inducing membrane fusion. Pdf the structure, function, and inhibition of influenza virus. Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell.
Vaccination and the use of neuraminidase inhibitors nais are currently the front lines of defense against seasonal influenza. Neuraminidase hemagglutinin abstract practical methods to measure the potency of in. Antigenic drift of hemagglutinin and neuraminidase in. 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. 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. Hemagglutinin designated as ha and neuraminidase designated as na are glycoproteins. These vaccines have long been evaluated based on the antibody response they elicit, particularly to the viral hemagglutinin ha 1, 2. The hemagglutinin ha is a prime determinant of the pathogenicity of influenza a viruses. Expression of functional recombinant hemagglutinin and. 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. Hemagglutininneuraminidase refers to a single viral protein that has both hemagglutinin and endo neuraminidase ec 3. Influenza virus haemagglutinin ha and neuraminidase na are.
This resulted in a clear separation of hemagglutinin and neuraminidase activities and. 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. An analysis of the role of neuraminidase in the receptor. Proteolytic activation of the hemagglutinin as a fusion protein has been known for. The molecular characterizations of surface proteins hemagglutinin and. Influenzahemagglutininand neuraminidasemembrane glycoproteins. Inhibition of neuraminidase by ganoderma triterpenoids and. Sep 10, 2010 the two glycoproteins of the influenza virus membrane, hemagglutinin ha 3 and neuraminidase na, both recognize sialic acid 1, 3. Mumps virus is one of the main cause of respiratory illnesses in humans, especially children.
Broad and protective influenza b virus neuraminidase. View fulltext html download pdf track your manuscript. Numerous ha substitutions have been identified in nonclinical nai resistanceselection experiments as well as in clinical. The influenza virus major surface glycoproteins, hemagglutinin ha, and.
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