HPeV3 structural and functional studies (HPEV3 STRUCTURE)
HPeV3 structural and functional studies
Date du début: 1 août 2014,
Date de fin: 31 juil. 2016
Human parechovirus 3 (HPeV3) belongs to the genus Parechovirus within the large and growing family of Picornaviridae. Currently, the Picornaviridae family contains 37 species grouped into 17 genera. All picornaviruses are small icosahedrally-symmetric non-enveloped viruses that possess single-stranded, positive-sense RNA genomes. Picornaviruses, including parechoviruses, contain significant human pathogens that can cause a wide range of disease symptoms. Parechoviruses mainly cause asymptomatic or mild infections primarily in small children. Recently, however, there have been many case reports describing parechovirus association with encephalitis, meningitis and neonatal sepsis. Due to the relatively simple protein components of parechovirus (just three major capsid proteins which are highly variable, and some very conserved non-structural proteins), the majority of the variation in disease is associated with the variation in the capsid proteins.The entry pathway of parechoviruses is poorly understood. In general the understanding on picornavirus entry is built on the evidence obtained from a few model viruses. The HPeV1 life cycle starts via binding of the virus to integrin receptor(s) on the surface of the host cell; then follows virus internalization via clathrin-mediated endocytosis and transport of the virus in endosomal vesicles to the site of replication in the cell interior. HPeV1 binds to two integrins, αVβ3 and αVβ6, via its RGD motif located in VP1 on the capsid. HPeV3 does not possess a RGD motif thus further studies are needed to elucidate the HPeV3 entry pathway. This project aims to unravel structural and biological properties of HPeV3 to facilitate a progress in parechovirus diagnostic and treatment. Such highly innovative methods as cryo EM, CEMOVIS and 3D organ culture will be applied.
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