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

doi:10.1111/j.1462-5822.2009.01385.x

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

Journal article

Open access

Peer reviewed

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 and Christopher F Basler

Cellular microbiology, Vol.12(2), pp.148-157

02/2010

DOI: 10.1111/j.1462-5822.2009.01385.x

PMCID: PMC2996272

PMID: 19775255

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Abstract

Cathepsins B and L contribute to Ebola virus (EBOV) entry into Vero cells and MEFs. 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 beta-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 pretreated for 48 hours 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.

Details

Title: Subtitle: Zaire Ebola virus entry into human dendritic cells is insensitive to cathepsin L inhibition
Creators: Osvaldo Martinez - Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
Joshua Johnson - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland
Balaji Manicassamy - Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
Lijun Rong - Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60607
Gene G Olinger - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland
Lisa E Hensley - U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland
Christopher F Basler - Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
Resource Type: Journal article
Publication Details: Cellular microbiology, Vol.12(2), pp.148-157
DOI: 10.1111/j.1462-5822.2009.01385.x
PMID: 19775255
PMCID: PMC2996272
ISSN: 1462-5814
eISSN: 1462-5822
Language: English
Date published: 02/2010
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083872802771

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