Journal ArticleDOI
Ebola and Marburg Viruses Replicate in Monocyte-Derived Dendritic Cells without Inducing the Production of Cytokines and Full Maturation
Catharine M. Bosio,M. Javad Aman,Case C. Grogan,Robert J. Hogan,Gordon Ruthel,Diane L. Negley,Mansour Mohamadzadeh,Sina Bavari,Alan L. Schmaljohn +8 more
TLDR
It is demonstrated that EBOV and MARV infected and replicated in primary human DCs without inducing cytokine secretion, and DCs are disabled, and an effective early host response is delayed by the necessary reliance on less-efficient secondary mechanisms.Abstract:
Ebola virus (EBOV) and Marburg virus (MARV) cause rapidly progressive hemorrhagic fever with high mortality and may possess specialized mechanisms to evade immune destruction. We postulated that immune evasion could be due to the ability of EBOV and MARV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. We demonstrate that EBOV and MARV infected and replicated in primary human DCs without inducing cytokine secretion. Infected DC cultures supported exponential viral growth without releasing interferon (IFN)-alpha and were impaired in IFN-alpha production if treated with double-stranded RNA. Moreover, EBOV and MARV impaired the ability of DCs to support T cell proliferation, and infected, immature DCs underwent an anomalous maturation. These findings may explain the profound virulence of EBOV and MARV--DCs are disabled, and an effective early host response is delayed by the necessary reliance on less-efficient secondary mechanisms.read more
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Journal ArticleDOI
Ebola haemorrhagic fever
TL;DR: Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock.
Journal ArticleDOI
Ebola Virus VP35 Protein Binds Double-Stranded RNA and Inhibits Alpha/Beta Interferon Production Induced by RIG-I Signaling
Washington B. Cárdenas,Yueh Ming Loo,Michael Gale,Amy L. Hartman,Christopher R. Kimberlin,Luis Martinez-Sobrido,Erica Ollmann Saphire,Christopher F. Basler +7 more
TL;DR: Evidence is provided that VP35 possesses double-stranded RNA (dsRNA)-binding activity, which supports the hypothesis that dsRNA binding may contribute to VP35 IFN antagonist function, and that additional mechanisms of inhibition, at a point proximal to the IRF-3 kinases, most likely also exist.
Journal ArticleDOI
Ebola Virus VP24 Binds Karyopherin α1 and Blocks STAT1 Nuclear Accumulation
St. Patrick Reid,Lawrence W. Leung,Amy L. Hartman,Osvaldo Martinez,Megan L. Shaw,Caroline Carbonnelle,Viktor E. Volchkov,Stuart T. Nichol,Christopher F. Basler +8 more
TL;DR: It is demonstrated that the EBOV VP24 protein functions as an inhibitor ofIFN-α/β and IFN-γ signaling, and is likely to be an important virulence determinant that allows E BOV to evade the antiviral effects of IFNs.
Journal ArticleDOI
DC-SIGN and DC-SIGNR Interact with the Glycoprotein of Marburg Virus and the S Protein of Severe Acute Respiratory Syndrome Coronavirus
Andrea Marzi,Thomas Gramberg,Graham Simmons,Peggy Möller,Andrew J. Rennekamp,Mandy Krumbiegel,Martina Geier,Jutta Eisemann,Nadine Turza,Bertrand Saunier,Alexander Steinkasserer,Stephan Becker,Paul Bates,Heike Hofmann,Stefan Pöhlmann +14 more
TL;DR: DC-SIGN and DC-SIGNR enhance infection mediated by the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus and might promote viral dissemination.
Journal ArticleDOI
Human Fatal Zaire Ebola Virus Infection Is Associated with an Aberrant Innate Immunity and with Massive Lymphocyte Apoptosis
TL;DR: This work showed that fatal outcome is associated with aberrant innate immune responses and with global suppression of adaptive immunity, and the innate immune reaction was characterized by a “cytokine storm,” with hypersecretion of numerous proinflammatory cytokines, chemokines and growth factors.
References
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Journal ArticleDOI
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