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Proteolytic Activation of Paramyxoviruses and Pneumoviruses

  • Everett Clinton Smith
  • Rebecca Ellis Dutch
Chapter

Abstract

Viruses in the families Paramyxoviridae and Pneumoviridae infect multiple animal species, and infection can result in varying disease severity. Membrane fusion is an obligate early step during infection and is driven primarily by viral fusion (F) proteins present on the viral envelope. F-mediated membrane fusion begins with insertion of a hydrophobic fusion peptide into the cell membrane and, through a series of conformational changes, culminates in the merger of both the viral and cellular membranes. Proteolytic processing N-terminal to the fusion peptide enables insertion into the cellular membrane, making this cleavage event an essential step in F-promoted membrane fusion. While all F proteins are cleaved by host proteases, the protease utilized and location of F cleavage vary widely among paramyxo- and pneumoviruses. With some paramyxoviruses, proteolytic activation of the hemagglutinin-neuraminidase (HN) glycoprotein has also been observed involving removal of a C-terminal extension from a precursor that blocks the attachment function of this protein. The availability of protein structures and extensive studies on the spatial and temporal processing details have illuminated many important aspects of proteolytic activation of these proteins. However, why such disparate proteolytic cleavage pathways evolved and to what extent they affect pathogenesis are less well understood.

Keywords

Paramyxovirus Pneumovirus Proteolytic cleavage Furin Cathepsin Fusion protein Membrane fusion Measles virus Mumps virus Hendra virus Nipah virus Respiratory syncytial virus Human metapneumovirus 

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiologyUniversity of the SouthSewaneeUSA
  2. 2.Department of Molecular and Cellular BiochemistryUniversity of KentuckyLexingtonUSA

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