Interaction between Ebola virus glycoprotein and host Toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1

Okumura Atsushi, Paula M. Pitha, Akihiko Yoshimura, Ronald N. Harty

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Abstract

Ebola virus initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. These inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal Ebola virus infections. Here we report that host Toll-like receptor 4 (TLR4) is a sensor for Ebola virus glycoprotein (GP) on virus-like particles (VLPs) and that resultant TLR4 signaling pathways lead to the production of proinflammatory cytokines and suppressor of cytokine signaling 1 (SOCS1) in a human monocytic cell line and in HEK293-TLR4/MD2 cells stably expressing the TLR4/MD2 complex. Ebola virus GP was found to interact with TLR4 by immunoprecipitation/Western blot analyses, and Ebola virus GP on VLPs was able to stimulate expression of NF-κB in a TLR4-dependent manner. Interestingly, we found that budding of Ebola virus VLPs was more pronounced in TLR4-stimulated cells than in unstimulated control cells. In sum, these findings identify the host innate immune protein TLR4 as a sensor for Ebola virus GP which may play an important role in the immunopathogenesis of Ebola virus infection.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalJournal of Virology
Volume84
Issue number1
DOIs
Publication statusPublished - 2010 Jan

Fingerprint

Ebolavirus
Toll-Like Receptor 4
glycoproteins
Glycoproteins
cytokines
Cytokines
virus-like particles
Ebola Hemorrhagic Fever
Virion
Toll-like receptor 4
cells
chemokines
Chemokines
Immunoprecipitation
infection
monocytes
Monocytes
Shock
Western blotting
macrophages

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Interaction between Ebola virus glycoprotein and host Toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. / Atsushi, Okumura; Pitha, Paula M.; Yoshimura, Akihiko; Harty, Ronald N.

In: Journal of Virology, Vol. 84, No. 1, 01.2010, p. 27-33.

Research output: Contribution to journalArticle

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