No role for pepstatin-A-sensitive acidic proteinases in reovirus infections of L or MDCK cells

Virology. 1998 Nov 25;251(2):264-72. doi: 10.1006/viro.1998.9434.


Strong evidence indicates that virions of mammalian reoviruses undergo proteolytic processing by acid-dependent cellular proteinases as an essential step in productive infection. Proteolytic processing takes the form of a series of cleavages of outer-capsid proteins final sigma3 and mu1/mu1C. Previous studies showed an effect of both NH4Cl and E-64 on these cleavages, indicating that one or more of the acid-dependent cysteine proteinases in mammalian cells (cathepsins B and L, for example) is required; however, these studies did not address whether acid-dependent aspartic proteinases in those cells (cathepsin D, for example) may also be required. To determine the role of aspartic proteinases in reovirus entry, studies with pepstatin A, a specific inhibitor of aspartic proteinases, were performed. The results showed that pepstatin A neither blocks nor slows reovirus infection of L or MDCK cells. Experiments using ribonuclease A and other proteins as cleavable substrates showed that cathepsin-D-like proteinases from these cells are inhibited within the tested range of pepstatin A concentrations both in vitro and within living cells. In other experiments, virion-bound final sigma3 protein was shown to be a poor substrate for cleavage by cathepsin D in vitro, consistent with the findings with inhibitors. In sum, the data indicate that cathepsin-D-like aspartic proteinases provide little or no activity toward proteolytic events required for infection of L or MDCK cells with reovirus virions.

Publication types

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

MeSH terms

  • Animals
  • Capsid / metabolism
  • Capsid Proteins*
  • Cathepsin D / antagonists & inhibitors
  • Cathepsin D / physiology*
  • Cell Line
  • Dogs
  • Kidney / virology
  • L Cells
  • Mice
  • Pepstatins / pharmacology*
  • Protease Inhibitors / pharmacology*
  • RNA-Binding Proteins / metabolism
  • Reoviridae / drug effects
  • Reoviridae / growth & development
  • Reoviridae / pathogenicity*
  • Ribonuclease, Pancreatic / metabolism
  • Virion / metabolism


  • Capsid Proteins
  • Pepstatins
  • Protease Inhibitors
  • RNA-Binding Proteins
  • sigma protein 3, Reovirus
  • Streptomyces pepsin inhibitor
  • Ribonuclease, Pancreatic
  • Cathepsin D
  • pepstatin