Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System

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Human coronaviruses (HCoV) are respiratory pathogens involved in a sizable proportion of common colds. They have over the years been associated with the development of neurological diseases, given their demonstrated neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein appears to be associated with these neurologic features and is a major factor of virulence for several coronavirus species, including HCoV-OC43. To further characterize the role of this protein in neurovirulence and virus spread within the CNS, we sought to identify amino acid residues that may be important for this function. Our data revealed that one of them, G758R, introduces a functional furin-like cleavage site in the S protein (RRSR↓R758). This change in S protein mostly impacts neurovirulence, which seems associated with a modified viral dissemination, without significantly affecting its neuroinvasive capacity. This mutation, found in all characterized contemporary human clinical respiratory isolates, underlines previous findings that naturally existing field isolates of HCoV-OC43 variants still possess the capacity to invade the CNS where they could eventually adapt and establish a persistent human CNS infection, a mechanism potentially associated with human encephalitis or neurodegenerative pathologies of unknown etiologies.

Vyšlo v časopise: Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005261
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005261

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