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Proteolytic Activation of Paramyxoviruses and Pneumoviruses

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Activation of Viruses by Host Proteases

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.

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Authors and Affiliations

  1. Department of Biology, University of the South, Sewanee, TN, USA

    Everett Clinton Smith

  2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA

    Rebecca Ellis Dutch

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  1. Institut für Virologie, Philipps Universität, Marburg, Germany

    Eva Böttcher-Friebertshäuser

  2. Institut für Virologie, Philipps Universität, Marburg, Germany

    Wolfgang Garten

  3. Institut für Virologie, Philipps-Universität, Marburg, Germany

    Hans Dieter Klenk

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Smith, E.C., Dutch, R.E. (2018). Proteolytic Activation of Paramyxoviruses and Pneumoviruses. In: Böttcher-Friebertshäuser, E., Garten, W., Klenk, H. (eds) Activation of Viruses by Host Proteases. Springer, Cham. https://doi.org/10.1007/978-3-319-75474-1_2

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