Parainfluenza virus type 3 hemagglutinin-neuraminidase

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Like influenza, the paramyxoviruses show hemagglutinin and neuraminidase (HN) activities, but in this case, the two activities reside on the same glycoprotein. Structures of three paramyxovirus HNs have been determined; they are Newcastle Disease virus, human parainfluenza type 3, and human parainfluenza type 5 (formerly called SV5). The structures show an identical fold to influenza neuraminidase, with an NA active site that is almost identical to that of influenza. Thus HN is a sialidase that also binds sialylated glycans as receptors for cell entry. Whether there is a separate binding site has been a subject of great controversy that is still not solved. NDV shows sialic acid bound at a second site but the second molecule has not been seen in hPIV3 or hPIV5 HN structures. Mutagenesis and antibody studies suggest one site in some strains and two sites in others, while a second site appeared to be created in hPIV3 by mutagenesis. This lack of understanding of how paramyoviruses enter cells and how new viruses are released has severely hampered development to antivirals targeted to these activities. CFG PIs are investigating the binding and cleavage specificities of HNs and mutants.

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) contributing to the understanding of parainfluenza virus type 3 HN include: Gillian Air, Theodore Jardetsky, Matteo Porotto, Charles Russell

Progress toward understanding this GBP paradigm

Carbohydrate ligands

Parainfluenza virus type 3 hemagglutinin-neuraminidase binds sialylated glycans.

Cellular expression of GBP and ligands

Parainfluenza virus type 3 hemagglutinin-neuraminidase is expressed by paramyxoviruses.

Biosynthesis of ligands


Structure


Biological roles of GBP-ligand interaction


CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for "parainfluenza".

Glycan profiling


Glycogene microarray


Knockout mouse lines


Glycan array

There have been many resource requests for glycan array screening of paramyxovirus hemagglutinin-neuraminidase [1]. To see all glycan array results for paramyxovirus hemagglutinin-neuraminidase, click here.

Related GBPs

  • Other paramyxovirus HNs: some appear to have one site that carries out both activities; others appear to have separate sites.
  • Human parainfluenza types 1, 2, 4 and 5
  • Newcastle Disease virus
  • Mumps virus

References


Acknowledgements

The CFG is grateful to the following PIs for their contributions to this wiki page: Gillian Air, James Paulson, Matteo Porotto

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