Cleavage of the Glycoprotein of Arenaviruses

  • Antonella Pasquato
  • Laura Cendron
  • Stefan KunzEmail author


The arenaviruses are a large family of emerging negative-stranded RNA viruses that include several severe human pathogens causing hemorrhagic fevers with high mortality. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P is a key factor for zoonotic transmission and human disease potential. Apart from being an essential host factor for arenavirus infection, SKI-1/S1P is involved in the regulation of important physiological processes and linked to major human diseases. This chapter provides an overview of the mechanisms of arenavirus GPC processing by SKI-1/S1P including recent findings. We will highlight to what extent the molecular mechanisms of SKI-1/S1P cleavage of viral GPC differ from processing of SKI-1/S1P’s cellular substrates and discuss the implications for virus-host interaction and coevolution. Moreover, we will show how the use of the viral GPC as a “molecular probe” uncovered novel and unusual aspects of SKI-1/S1P biosynthesis and maturation. The crucial role of SKI-1/S1P in arenavirus infection and other major human diseases combined with its nature as an enzyme makes SKI-1/S1P further an attractive target for therapeutic intervention. In the last part, we will therefore cover past and present efforts to identify specific SKI-1/S1P inhibitors.


Old World arenaviruses New World arenaviruses Lassa virus Machupo virus Junin virus Glycoprotein Proprotein convertases Proteolytic processing Maturation SKI-1/S1P Drug screening SKI-1/S1P sensor 



The authors would like to apologize to all those colleagues whose excellent work could not be covered due to space limitations. This work was supported by Swiss National Science Foundation grant 310030_170108 to S.K. and funds to S.K. from the University of Lausanne.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Antonella Pasquato
    • 1
  • Laura Cendron
    • 2
  • Stefan Kunz
    • 1
    Email author
  1. 1.Lausanne University HospitalInstitute of MicrobiologyLausanneSwitzerland
  2. 2.Department of BiologyUniversity of PadovaPadovaItaly

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