Zaire Ebola virus entry into human dendritic cells is insensitive to cathepsin L inhibition

Osvaldo Martinez, Joshua Johnson, Balaji Manicassamy, Lijun Rong, Gene G. Olinger, Lisa E. Hensley, Christopher F. Basler

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Cathepsins B and L contribute to Ebola virus (EBOV) entry into Vero cells and mouse embryonic fibroblasts. However, the role of cathepsins in EBOV-infection of human dendritic cells (DCs), important targets of infection in vivo, remains undefined. Here, EBOV-like particles containing a β-lactamase-VP40 fusion reporter and Ebola virus were used to demonstrate the cathepsin dependence of EBOV entry into human monocyte-derived DCs. However, while DC infection is blocked by cathepsin B inhibitor, it is insensitive to cathepsin L inhibitor. Furthermore, DCs pre-treated for 48 h with TNFα were generally less susceptible to entry and infection by EBOV. This decrease in infection was associated with a decrease in cathepsin B activity. Thus, cathepsin L plays a minimal, if any, role in EBOV infection in human DCs. The inflammatory cytokine TNFα modulates cathepsin B activity and affects EBOV entry into and infection of human DCs.

Original languageEnglish (US)
Pages (from-to)148-157
Number of pages10
JournalCellular Microbiology
Volume12
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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