Hemagglutination can be used to identify RBC surface antigens (with known antibodies) or to screen for antibodies (with RBCs with known surface antigens).
Using anti-A and anti-B antibodies that bind specifically to either the A or to the B blood group surface antigens on RBCs it is possible to test a small sample of blood and determine the ABO blood group (or blood type) of an individual.
The bedside card method of blood grouping relies on visual agglutination to determine an individual's blood group. The card has dried blood group antibody reagents fixed onto its surface and a drop of the individual's blood is placed on each area on the card. The presence or absence of visual agglutination enables a quick and convenient method of determining the ABO and Rhesus status of the individual.
Agglutination of red blood cells is used in the Coombs test.
Antigenic drift is a mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites. This results in a new strain of virus particles which cannot be inhibited as effectively by the antibodies that were originally targeted against previous strains, making it easier for the virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.
The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific immune receptors, which prevent re-infection by this particular strain of the virus and produce acquired immunity. Similarly, a vaccine against a virus works by teaching the immune system to recognize the antigens exhibited by this virus. However, viral genomes are constantly mutating, producing new forms of these antigens. If one of these new forms of an antigen is sufficiently different from the old antigen, it will no longer bind to the receptors of the body cells, and viruses with these new antigens can infect the body cell as it avoids the immunity to the original strain of the virus. When such a change occurs, people who have had the illness in the past are therefore not immune to the new strain of the virus (as the new strain of the virus has a different antigen which the body cell cannot recognise) and thus the vaccines against the original virus will be less effective against the illness. Two processes drive the antigens to change: antigenic drift and antigenic shift, antigenic drift being the more common. The rate of antigenic drift is dependent on two characteristics: the duration of the epidemic, and the strength of host immunity. A longer epidemic allows for selection pressure to continue over an extended period of time and stronger host immune responses increase selection pressure for development of novel antigens.Avulavirus
The genus Avulavirus is one of seven genera in the family Paramyxoviridae and contains viruses that used to be classified in the genus Rubulavirus. In contrast to rubulaviruses, avulaviruses infect birds (hence the name "avulaviruses", a contraction of "avian rubulavirus") and translate protein V from an edited RNA transcript. Avulaviruses have a hemagglutinin-neuraminidase attachment protein and do not produce a non-structural protein C. The most important and best characterized avulavirus is Newcastle disease virus, a variant of avian paramyxovirus 1 (species Avian avulavirus 1). Avulaviruses can be separated into distinct serotypes using hemagglutination assay and neuraminidase assay. All avulaviruses hemagglutinate chicken RBCs except for avian paramyxovirus 5 which does not hemagglutinate RBCs from any species. Avian paramyxovirus 6 is unique to the presence of the SH gene between the F and HN genes. Avian paramyxovirus 11 has the longest genome among the APMVs.Cold agglutinin disease
Cold agglutinin disease is an autoimmune disease characterized by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells, causing them to agglutinate and undergo lysis. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C.
Cold agglutinin disease was first described in 1957.Filamentous haemagglutinin adhesin
The filamentous haemagglutinin adhesin (FHA) is a large, filamentous protein that serves as a dominant attachment factor for adherence to host ciliated epithelial cells of the respiratory tract, called respiratory epithelium. It is associated with biofilm formation and possesses at least four binding domains which can bind to different cell receptors on the epithelial cell surface. One notable bacterium that produces filamentous hæmagglutinin adhesin is Bordetella pertussis, which uses this protein as a virulence factor.H5N1 genetic structure
H5N1 genetic structure is the molecular structure of the H5N1 virus's RNA.
H5N1 is an Influenza A virus subtype. Experts believe it might mutate into a form that transmits easily from person to person. If such a mutation occurs, it might remain an H5N1 subtype or could shift subtypes as did H2N2 when it evolved into the Hong Kong Flu strain of H3N2.
H5N1 has mutated through antigenic drift into dozens of highly pathogenic varieties, but all currently belonging to genotype Z of avian influenza virus H5N1. Genotype Z emerged through reassortment in 2002 from earlier highly pathogenic genotypes of H5N1 that first appeared in China in 1996 in birds and in Hong Kong in 1997 in humans. The "H5N1 viruses from human infections and the closely related avian viruses isolated in 2004 and 2005 belong to a single genotype, often referred to as genotype Z." This infection of humans coincided with an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong’s poultry population. This panzootic (a disease affecting animals of many species especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. The name H5N1 refers to the subtypes of surface antigens present on the virus: hemagglutinin type 5 and neuraminidase type 1.
Genotype Z of H5N1 is now the dominant genotype of H5N1. Genotype Z is endemic in birds in southeast Asia and represents a long term pandemic threat.
Influenza A viruses have 11 genes on eight separate RNA molecules :
PB2 (polymerase basic 2)
PB1 (polymerase basic 1)
PB1-F2 (alternate open reading frame near the 5' end of the PB1 gene)
PA (polymerase acidic)
M1 and M2 (matrix)
NEP/NS2 (nuclear export of vRNPs)Two of the most important RNA molecules are HA and PB1. HA creates a surface antigen that is especially important in transmissibility. PB1 creates a viral polymerase molecule that is especially important in virulence.
The HA RNA molecule contains the HA gene, which codes for hemagglutinin, which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to cells. This attachment is required for efficient transfer of flu virus genes into cells, a process that can be blocked by antibodies that bind to the hemagglutinin proteins.
One genetic factor in distinguishing between human flu viruses and avian flu viruses is that avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors. Humans have avian-type receptors at very low densities and chickens have human-type receptors at very low densities. Some isolates taken from H5N1-infected human have been observed to have HA mutations at positions 182, 192, 223, 226, or 228 and these mutations have been shown to influence the selective binding of the virus to those previously mentioned sialic acid avian and/or human cell surface receptors. These are the types of mutations that can change a bird flu virus into a flu pandemic virus.
A 2008 virulence study that mated in a laboratory an avian flu H5N1 virus that circulated in Thailand in 2004 and a human flu H3N2 virus recovered in Wyoming in 2003 produced 63 viruses representing various potential combinations of human and avian influenza A virus genes. One in five were lethal to mice at low doses. The virus that most closely matched H5N1 for virulence was one with the hemagglutinin (HA), the neuraminidase (NA) and the PB1 avian flu virus RNA molecules with their genes combined with the remaining five RNA molecules (PB2, PA, NP, M, and NS) with their genes from the human flu virus. Both the viruses from the 1957 pandemic and 1968 pandemic carried an avian flu virus PB1 gene. The authors suggest that picking up an avian flu virus PB1 gene may be a critical step in a potential flu pandemic virus arising through reassortment."PB1 codes for the PB1 protein and the PB1-F2 protein. The PB1 protein is a critical component of the viral polymerase. The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis. [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza." This was discovered by Chen et al. and reported in Nature. "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus."H5N1 vaccine
A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1.
Vaccines have been formulated against several of the avian H5N1 influenza varieties. Vaccination of poultry against the ongoing H5N1 epizootic is widespread in certain countries. Some vaccines also exist for use in humans, and others are in testing, but none have been made available to civilian populations, nor produced in quantities sufficient to protect more than a tiny fraction of the Earth's population in the event of an H5N1 pandemic.
Three H5N1 vaccines for humans have been licensed as of June 2008:
Sanofi Pasteur's vaccine approved by the United States in April 2007,
GlaxoSmithKline's vaccine Prepandrix approved by the European Union in May 2008, with reactive AS03 (containing squalene) adjuvant. and
CSL Limited's vaccine Panvax approved by Australia in June 2008.In November 2013, the FDA approved an experimental H5N1 bird flu vaccine to be held in stockpiles. In a clinical trial including 3,400 adults, 91% of people age 18-64 and 74% of people age 65 or older formed an immune response sufficient to provide protection. Reported adverse effects were generally mild, with pain at the injection site being the most common adverse effect.All are produced in eggs and would require many months to be altered to a pandemic version.
H5N1 continually mutates, meaning vaccines based on current samples of avian H5N1 cannot be depended upon to work in the case of a future pandemic of H5N1. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University, has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.
Problems with H5N1 vaccine production include:
lack of overall production capacity
lack of surge production capacity (it is impractical to develop a system that depends on hundreds of millions of 11-day-old specialized eggs on a standby basis)
the pandemic H5N1 might be lethal to chickensCell culture (cell-based) manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines and thereby solve the problems associated with creating flu vaccines using chicken eggs as is currently done.:
Currently, influenza vaccine for the annual, seasonal influenza program comes from four manufacturers. However, only a single manufacturer produces the annual vaccine entirely within the U.S. Thus, if a pandemic occurred and existing U.S.-based influenza vaccine manufacturing capacity was completely diverted to producing a pandemic vaccine, supply would be severely limited. Moreover, because the annual influenza manufacturing process takes place during most of the year, the time and capacity to produce vaccine against potential pandemic viruses for a stockpile, while continuing annual influenza vaccine production, is limited. Since supply will be limited, it is critical for HHS to be able to direct vaccine distribution in accordance with predefined groups (see Appendix D); HHS will ensure the building of capacity and will engage states in a discussion about the purchase and distribution of pandemic influenza vaccine.Vaccine production capacity: The protective immune response generated by current influenza vaccines is largely based on viral hemagglutinin (HA) and neuraminidase (NA) antigens in the vaccine. As a consequence, the basis of influenza vaccine manufacturing is growing massive quantities of virus in order to have sufficient amounts of these protein antigens to stimulate immune responses. Influenza vaccines used in the United States and around world are manufactured by growing virus in fertilized hens' eggs, a commercial process that has been in place for decades. To achieve current vaccine production targets millions of 11-day old fertilized eggs must be available every day of production.In the near term, further expansion of these systems will provide additional capacity for the U.S.-based production of both seasonal and pandemic vaccines, however, the surge capacity that will be needed for a pandemic response cannot be met by egg-based vaccine production alone, as it is impractical to develop a system that depends on hundreds of millions of 11-day old specialized eggs on a standby basis. In addition, because a pandemic could result from an avian influenza strain that is lethal to chickens, it is impossible to ensure that eggs will be available to produce vaccine when needed.In contrast, cell culture manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines (e.g., polio vaccine, measles-mumps-rubella vaccine, chickenpox vaccine). In this system, viruses are grown in closed systems such as bioreactors containing large numbers of cells in growth media rather than eggs. The surge capacity afforded by cell-based technology is insensitive to seasons and can be adjusted to vaccine demand, as capacity can be increased or decreased by the number of bioreactors or the volume used within a bioreactor. In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be used in case of an influenza pandemic of H5N1 avian influenza and is conducting clinical trials with these vaccines. Researchers at the University of Pittsburgh have had success with a genetically engineered vaccine that took only a month to make and completely protected chickens from the highly pathogenic H5N1 virus.According to the United States Department of Health & Human Services:
In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. Dose-sparing technologies. Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies.Chiron Corporation is now recertified and under contract with the National Institutes of Health to produce 8,000–10,000 investigational doses of Avian Flu (H5N1) vaccine. MedImmune and Aventis Pasteur are under similar contracts. The United States government hopes to obtain enough vaccine in 2006 to treat 4 million people. However, it is unclear whether this vaccine would be effective against a hypothetical mutated strain that would be easily transmitted through human populations, and the shelflife of stockpiled doses has yet to be determined.The New England Journal of Medicine reported on March 30, 2006 on one of dozens of vaccine studies currently being conducted. The Treanor et al. study was on vaccine produced from the human isolate (A/Vietnam/1203/2004 H5N1) of a virulent clade 1 influenza A (H5N1) virus with the use of a plasmid rescue system, with only the hemagglutinin and neuraminidase genes expressed and administered without adjuvant. "The rest of the genes were derived from an avirulent egg-adapted influenza A/PR/8/34 strain. The hemagglutinin gene was further modified to replace six basic amino acids associated with high pathogenicity in birds at the cleavage site between hemagglutinin 1 and hemagglutinin 2. Immunogenicity was assessed by microneutralization and hemagglutination-inhibition assays with the use of the vaccine virus, although a subgroup of samples were tested with the use of the wild-type influenza A/Vietnam/1203/2004 (H5N1) virus." The results of this study combined with others scheduled to be completed by spring 2007 is hoped will provide a highly immunogenic vaccine that is cross-protective against heterologous influenza strains.On August 18, 2006. the World Health Organization changed the H5N1 strains recommended for candidate vaccines for the first time since 2004. "The WHO's new prototype strains, prepared by reverse genetics, include three new H5N1 subclades. The hemagglutinin sequences of most of the H5N1 avian influenza viruses circulating in the past few years fall into two genetic groups, or clades. Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections:
Subclade 1, Indonesia
Subclade 2, Middle East, Europe, and Africa
Subclade 3, ChinaOn the basis of the three subclades, the WHO is offering companies and other groups that are interested in pandemic vaccine development these three new prototype strains:
An A/Indonesia/2/2005-like virus
An A/Bar headed goose/Quinghai/1A/2005-like virus
An A/Anhui/1/2005-like virus[...] Until now, researchers have been working on prepandemic vaccines for H5N1 viruses in clade 1. In March, the first clinical trial of a U.S. vaccine for H5N1 showed modest results. In May, French researchers showed somewhat better results in a clinical trial of an H5N1 vaccine that included an adjuvant. Vaccine experts aren't sure if a vaccine effective against known H5N1 viral strains would be effective against future strains. Although the new viruses will now be available for vaccine research, WHO said clinical trials using the clade 1 viruses should continue as an essential step in pandemic preparedness, because the trials yield useful information on priming, cross-reactivity, and cross-protection by vaccine viruses from different clades and subclades."As of November 2006, the United States Department of Health and Human Services still had enough H5N1 pre-pandemic vaccine to treat about 3 million people (5.9 million full-potency doses) in spite of 0.2 million doses used for research and 1.4 million doses that have begun to lose potency (from the original 7.5 million full-potency doses purchased from Sanofi Pasteur and Chiron Corp.). The expected shelf life of seasonal flu vaccine is about a year so the fact that most of the H5N1 pre-pandemic stockpile is still good after about 2 years is considered encouraging.Hemagglutinin-neuraminidase
Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and neuraminidase activity. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins.
However it does show a structural similarity to influenza viral neuraminidase and has a six-bladed beta-propeller structure.Hemagglutinin-neuraminidase allows the virus to stick to a potential host cell, and cut itself loose if necessary.
Hemagglutinin-neuraminidase can be found in a variety of paramyxoviruses including mumps virus, human parainfluenza virus 3, and the avian pathogen Newcastle disease virus.
Parainfluenza hemagglutinin-neuraminidaseHemagglutinin-neuraminidase inhibitors have been investigated and suggest that there may applications for human use in the future.Hemagglutinin (influenza)
Influenza hemagglutinin (HA) or haemagglutinin[p] (British English) is a glycoprotein found on the surface of influenza viruses. Being a class I fusion protein, it is responsible for binding the virus to cells with sialic acid on the membranes, such as cells in the upper respiratory tract or erythrocytes. It is also responsible for the fusion of the viral envelope with the endosome membrane, after the pH has been reduced. The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro.Hemagglutinin esterase
Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as invading mechanism. HEs helps in the attachment and destruction of certain sialic acid receptors that are found on the host cell surface. Viruses that possess HEs include influenza C, Toro-viruses, and coronaviruses. HEs is a dimer transmembrane protein consisting of two monomers, each monomer is made of three domains. The three domains are: membrane fusion, esterase, and receptor binding domains.
The different HEs enzyme activities include: receptor binding activity, receptor hydrolysis (esterase) activity, and membrane fusion activity. The receptor binding activity involve the attachment of HEs to N-acetyl-9-O-acetylneuraminic acid (9-O-Ac- Neu5Ac) of glycolipids and glycoproteins and in turn serve as viral receptor.Receptor hydrolysis (esterase) activity allows virus particles to escape the infected cell by removing an acetyl group from the C9 position of terminal 9-O-Ac-Neu5Ac residues. Membrane fusion activity helps in incorporation viral genome into the host cell cytoplasm by enhancing the attachment between the viral envelope and host cell membrane.
In certain Influenza virus, the cell surface consists of both Hemagglutinin (HA) and Neuraminidase (NA) proteins that encompass enzymatic activities, whereas hemagglutinin-esterase fusion (HEF) proteins have been found to be the primary single spike protein that combines all of the enzymatic activities listed above. HEF proteins have been tested to be high-temperature and low-pH resistant and are the primary source of virulence in viruses.Influzena C have been shown to have unique HEF structure proteins that enhance its ability to infect the host cell compared to Influence A and B.
The folding of different domains in the hemagglutinin-esterase protein is important for intracellular transport of proteins from the endoplasmic reticulum to the Golgi apparatus. The presence of oligosaccharide chains in the E, F, and R domains of the HE enzyme also influence intracellular transport. Acylation of the hemagglutinin-esterase has shown to play an essential role in virus particle assembly replication. The exact process of enzyme catalytic cleavage has not yet been detailed out. However, proteolytic cleavage must occur before hemagglutinin-esterase membrane fusion activity. HEF proteins have a unique spikes hexagonal arrangement. This feature is unique to influenza C virus particles. The arrangement is a covering outside of the particle.Influenza A virus
Influenza A virus causes influenza in birds and some mammals, and is the only species of the Alphainfluenzavirus genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates of influenza A virus cause severe disease both in domestic poultry and, rarely, in humans. Occasionally, viruses are transmitted from wild aquatic birds to domestic poultry, and this may cause an outbreak or give rise to human influenza pandemics.Influenza A viruses are negative-sense, single-stranded, segmented RNA viruses.
The several subtypes are labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase). There are 18 different known H antigens (H1 to H18) and 11 different known N antigens (N1 to N11). H17N10 was isolated from fruit bats in 2012. H18N11 was discovered in a Peruvian bat in 2013.Each virus subtype has mutated into a variety of strains with differing pathogenic profiles; some are pathogenic to one species but not others, some are pathogenic to multiple species.
A filtered and purified influenza A vaccine for humans has been developed, and many countries have stockpiled it to allow a quick administration to the population in the event of an avian influenza pandemic. Avian influenza is sometimes called avian flu, and colloquially, bird flu. In 2011, researchers reported the discovery of an antibody effective against all types of the influenza A virus.Influenza A virus subtype H2N3
H2N3 is a subtype of the influenza A virus. Its name derives from the forms of the two kinds of proteins on the surface of its coat, hemagglutinin (H) and neuraminidase (N). H2N3 viruses can infect birds and mammals.Influenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called Influenza B virus.
Influenza B viruses are only known to infect humans and seals, giving them influenza. This limited host and range is apparently responsible for the lack of Influenzavirus B-caused influenza pandemics in contrast with those caused by the morphologically similar Influenzavirus A as both mutate by both antigenic drift and reassortment. Currently there are two co-circulating lineages of the Influenza B virus based on the antigenic properties of the surface glycoprotein hemagglutinin. The lineages are termed B/Yamagata/16/88-like and B/Victoria/2/87-like viruses. The quadrivalent influenza vaccine licensed by the CDC is currently designed to protect against both co-circulating lineages and has been shown to have greater effectiveness in prevention of influenza caused by Influenza B virus than the previous trivalent vaccine.Further diminishing the impact of this virus, "in humans, influenza B viruses evolve slower than A viruses and faster than C viruses". Influenzavirus B mutates at a rate 2 to 3 times slower than type A. Nevertheless, it is currently accepted that Influenza B viruses cause significant morbidity and mortality worldwide, and significantly impacts adolescents and schoolchildren.M1 protein
The M1 protein is a matrix protein of the influenza virus. It forms a coat inside the viral envelope. This is a bifunctional membrane/RNA-binding protein that mediates the encapsidation of RNA-nucleoprotein cores into the membrane envelope. It is therefore required that M1 binds both membrane and RNA simultaneously.The M1 protein binds to the viral RNA. The binding is not specific to any RNA sequence, and is performed via a peptide sequence rich in basic amino acids.
It also has multiple regulatory functions, performed by interaction with the components of the host cell. The mechanisms regulated include a role in the export of the viral ribonucleoproteins from the host cell nucleus, inhibition of viral transcription, and a role in the virus assembly and budding. The protein was found to undergo phosphorylation in the host cell.
The M1 protein forms a layer under the patches of host cell membrane that are rich with the viral hemagglutinin, neuraminidase and M2 transmembrane proteins, and facilitates budding of the mature viruses.
M1 consists of two domains connected by a linker sequence. The N-terminal domain has a multi-helical structure that can be divided into two subdomains. The C-terminal domain also contains alpha-helical structure.Measles hemagglutinin
Measles hemagglutinin is a hemagglutinin produced by measles virus.It attaches to CD46.Mumps hemagglutinin-neuraminidase
Mumps hemagglutinin-neuraminidase is a type of hemagglutinin-neuraminidase produced by mumps.Orthomyxoviridae
The Orthomyxoviruses (ὀρθός, orthós, Greek for "straight"; μύξα, mýxa, Greek for "mucus") are a family of RNA viruses that includes seven genera: Influenza virus A, Influenza virus B, Influenza virus C, Influenza virus D, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in vertebrates, including birds (see also avian influenza), humans, and other mammals. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates, such as ticks and mosquitoes.The four genera of Influenza virus, which are identified by antigenic differences in their nucleoprotein and matrix protein, infect vertebrates as follows:
Influenza virus A infects humans, other mammals, and birds, and causes all flu pandemics
Influenza virus B infects humans and seals
Influenza virus C infects humans, pigs, and dogs.
Influenza virus D infects pigs and cattleParainfluenza hemagglutinin-neuraminidase
Parainfluenza hemagglutinin-neuraminidase is a type of hemagglutinin-neuraminidase produced by parainfluenza.Tryptase
Tryptase (EC 22.214.171.124, ) is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase, which is believed to be responsible for cleaving the hemagglutinin surface protein of influenza A virus, thereby activating it and causing the symptoms of flu.Viral neuraminidase
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. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replication.
When influenza virus replicates, it attaches to the interior cell surface using hemagglutinin, a molecule found on the surface of the virus that binds to sialic acid groups. Sialic acids are found on various glycoproteins at the host cell surface, and the virus exploits these groups to bind the host cell. In order for the virus to be released from the cell, neuraminidase must enzymatically cleave the sialic acid groups from host glycoproteins.
Since the cleavage of the sialic groups is an integral part of influenza replication, blocking the function of neuraminidase with neuraminidase inhibitors is an effective way to treat influenza.
A single hemagglutinin-neuraminidase protein can combine neuraminidase and hemagglutinin functions, such as in mumps virus and human parainfluenza virus.