Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus

J Virol. 1995 May;69(5):3206-10. doi: 10.1128/JVI.69.5.3206-3210.1995.


We have identified the major cellular endoprotease that activates the fusion (F) glycoprotein of measles virus (MV) and have engineered a serine protease inhibitor (serpin) to target the endoprotease and inhibit the production of infectious MV. The F-protein precursor of MV was not cleaved efficiently into the mature F protein in human colon carcinoma cells lacking functional furin, indicating that furin is the major enzyme responsible for activation of the MV F protein. A human serpin alpha 1-antitrypsin variant was engineered to specifically inhibit furin. When expressed from a recombinant vaccinia virus in primate cells infected by MV, the engineered serpin (alpha 1-PDX) specifically inhibited furin-catalyzed cleavage of the F-protein precursor without affecting synthesis of other MV proteins. We generated human glioma cells stably expressing alpha 1-PDX. MV infection in these cells did not result in syncytia. The infected cells produced all the MV proteins, but the F-protein precursor remained largely uncleaved. This did not prevent virus assembly. However, the released virions contained inactive F-protein precursor rather than mature F protein, and infectious-virus titers were reduced by 3 to 4 orders of magnitude. These results show that a mature F protein is not required for the assembly of MV but is crucial for virus infectivity. The engineered serpin may offer a novel molecular antiviral approach against MV.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Cell Line
  • Cytopathogenic Effect, Viral / drug effects
  • Furin
  • HeLa Cells
  • Humans
  • Measles virus / drug effects*
  • Measles virus / growth & development
  • Measles virus / pathogenicity
  • Protein Engineering
  • Protein Processing, Post-Translational / drug effects
  • Serpins / genetics
  • Serpins / pharmacology*
  • Subtilisins / metabolism*
  • Viral Fusion Proteins / metabolism*
  • Virulence / drug effects


  • Antiviral Agents
  • Serpins
  • Viral Fusion Proteins
  • Subtilisins
  • Furin