Hemagglutinin-neuraminidase

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Hemagglutinin-neuraminidase, Paramyxoviridae
PDB 1usr EBI.jpg
Structure of the sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase. [1]
Identifiers
SymbolHN
Pfam PF00423
Pfam clan CL0434
InterPro IPR000665
SCOP2 1usr / SCOPe / SUPFAM
CAZy GH83
CDD cd15469
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1e8t , 1e8u , 1e8v , 1usr , 1usx , 1v2i , 1v3b , 1v3c , 1v3d , 1v3e

Hemagglutinin-neuraminidase refers to a single viral protein that has both hemagglutinin and (endo) neuraminidase EC 3.2.1.18 activity. This is in contrast to the proteins found in influenza, where both functions exist but in two separate proteins. Its neuraminidase domain has the CAZy designation glycoside hydrolase family 83 (GH83). [2]

It does show a structural similarity to influenza viral neuraminidase and has a six-bladed beta-propeller structure. [3] This Pfam entry also matches measles hemagglutinin (cd15467), which has a "dead" neuraminidase part repurposed as a receptor binding site. [4]

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.

Types include:

Hemagglutinin-neuraminidase inhibitors have been investigated and suggest that there may applications for human use in the future. [5]

Related Research Articles

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Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

<i>Paramyxoviridae</i> Family of viruses

Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, and 78 species, three genera of which are unassigned to a subfamily.

<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<i>Orthomyxoviridae</i> Family of RNA viruses including the influenza viruses

Orthomyxoviridae is a family of negative-sense RNA viruses. It includes seven genera: Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates. The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods).

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<i>Measles morbillivirus</i> Species of virus

Measles morbillivirus(MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is the cause of measles. Humans are the natural hosts of the virus; no animal reservoirs are known to exist.

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Exo-α-sialidase is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:

<span class="mw-page-title-main">Hemagglutinin esterase</span> Glycoprotein present in some enveloped viruses

Hemagglutinin esterase (HEs) is a glycoprotein that certain enveloped viruses possess and use as an 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 virus, toroviruses, and coronaviruses of the subgenus Embecovirus. 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.

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<i>Murine respirovirus</i> Sendai virus, virus of rodents

Murine respirovirus, formerly Sendai virus (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped, 150-200 nm–diameter, negative sense, single-stranded RNA virus of the family Paramyxoviridae. It typically infects rodents and it is not pathogenic for humans or domestic animals

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<span class="mw-page-title-main">Viral neuraminidase</span>

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. Neuraminidase inhibitors are antiviral agents that inhibit influenza viral neuraminidase activity and are of major importance in the control of influenza.

<span class="mw-page-title-main">Hemagglutinin</span>

In molecular biology, hemagglutinins are receptor-binding membrane fusion glycoproteins produced by viruses in the Paramyxoviridae family. Hemagglutinins are responsible for binding to receptors on red blood cells to initiate viral attachment and infection. The agglutination of red cells occurs when antibodies on one cell bind to those on others, causing amorphous aggregates of clumped cells.

Measles hemagglutinin is a hemagglutinin produced by measles virus.

Parainfluenza hemagglutinin-neuraminidase is a type of hemagglutinin-neuraminidase produced by parainfluenza.

<span class="mw-page-title-main">George Hirst (virologist)</span> American virologist and science administrator

George Keble Hirst, M.D. was an American virologist and science administrator who was among the first to study the molecular biology and genetics of animal viruses, especially influenza virus. He directed the Public Health Research Institute in New York City (1956–1981), and was also the founding editor-in-chief of Virology, the first English-language journal to focus on viruses. He is particularly known for inventing the hemagglutination assay, a simple method for quantifying viruses, and adapting it into the hemagglutination inhibition assay, which measures virus-specific antibodies in serum. He was the first to discover that viruses can contain enzymes, and the first to propose that virus genomes can consist of discontinuous segments. The New York Times described him as "a pioneer in molecular virology."

Neuraminidase inhibitors inhibit enzymatic activity of the enzyme neuraminidase (sialidase). These type of inhibitors have been introduced as anti-influenza drugs as they prevent the virus from exiting infected cells and thus stop further spreading of the virus. Neuraminidase inhibitors for human neuraminidase (hNEU) have the potential to be useful drugs as the enzyme plays a role in several signaling pathways in cells and is implicated in diseases such as diabetes and cancer.

Bat mumps orthorubulavirus, formerly Bat mumps rubulavirus (BMV), is a member of genus Orthorubulavirus, family Paramyxoviridae, and order Mononegavirales. Paramyxoviridae viruses were first isolated from bats using heminested PCR with degenerate primers. This process was then followed by Sanger sequencing. A specific location of this virus is not known because it was isolated from bats worldwide. Although multiple paramyxoviridae viruses have been isolated worldwide, BMV specifically has not been isolated thus far. However, BMV was detected in African fruit bats, but no infectious form has been isolated to date. It is known that BMV is transmitted through saliva in the respiratory system of bats. While the virus was considered its own species for a few years, phylogenetic analysis has since shown that it is a member of Mumps orthorubulavirus.

References

  1. Zaitsev V, von Itzstein M, Groves D, et al. (April 2004). "Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion". J. Virol. 78 (7): 3733–41. doi:10.1128/JVI.78.7.3733-3741.2004. PMC   371092 . PMID   15016893.
  2. Yuan P, Thompson TB, Wurzburg BA, Paterson RG, Lamb RA, Jardetzky TS (2005). "Structural studies of the parainfluenza virus 5 hemagglutinin-neuraminidase tetramer in complex with its receptor, sialyllactose". Structure. 13 (5): 803–15. doi: 10.1016/j.str.2005.02.019 . PMID   15893670.
  3. Lawrence MC, Borg NA, Streltsov VA, et al. (January 2004). "Structure of the haemagglutinin-neuraminidase from human parainfluenza virus type III". J. Mol. Biol. 335 (5): 1343–57. doi:10.1016/j.jmb.2003.11.032. PMID   14729348.
  4. Colf, LA; Juo, ZS; Garcia, KC (December 2007). "Structure of the measles virus hemagglutinin". Nature Structural & Molecular Biology. 14 (12): 1227–8. doi:10.1038/nsmb1342. PMID   18026116. S2CID   40292.
  5. Alymova IV, Taylor G, Takimoto T, et al. (May 2004). "Efficacy of novel hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 against human parainfluenza viruses in vitro and in vivo". Antimicrob. Agents Chemother. 48 (5): 1495–502. doi:10.1128/AAC.48.5.1495-1502.2004. PMC   400544 . PMID   15105096.