Suppressor of cytokine signaling 3 is an inducible host factor that regulates virus egress during Ebola virus infection

Atsushi Okumura, Angela L. Rasmussen, Peter Halfmann, Friederike Feldmann, Akihiko Yoshimura, Heinz Feldmann, Yoshihiro Kawaoka, Ronald N. Harty, Michael G. Katze

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Ebola virus (EBOV) 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 EBOV infections. The VP40 matrix protein is a key viral structural protein that is critical for virion egress. Physical and functional interactions between VP40 and host proteins such as Tsg101 and Nedd4 facilitate efficient release of VP40-driven viruslike particles (VLPs) and infectious virus. Here, we show that host suppressor of cytokine signaling 3 (SOCS3) can also bind to EBOV VP40, leading to enhanced ubiquitinylation and egress of VP40. Indeed, titers of infectious EBOV derived from SOCS3 knockout mouse embryonic fibroblasts (MEFs) were significantly reduced compared to those from wild-type (WT) MEFs at 24 and 48 h postinfection. Importantly, this reduced virus yield could be rescued back to WT levels by exogenously expressing SOCS3. Lastly, we show that SOCS3 expression is induced by EBOV glycoprotein (GP) expression and that VLPs containing EBOV VP40 and GP induced production of proinflammatory cytokines, which induced SOCS3 for negative-feedback regulation. These data indicate that host innate immune protein SOCS3 may play an important role in budding and pathogenesis of EBOV.

Original languageEnglish
Pages (from-to)10399-10406
Number of pages8
JournalJournal of Virology
Volume89
Issue number20
DOIs
Publication statusPublished - 2015

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Ebola Hemorrhagic Fever
Ebolavirus
Virus Release
cytokines
Cytokines
viruses
infection
Virion
Glycoproteins
fibroblasts
Fibroblasts
glycoproteins
Viral Structural Proteins
proteins
viral proteins
structural proteins
Chemokines
mice
Knockout Mice
chemokines

ASJC Scopus subject areas

  • Immunology
  • Virology

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Suppressor of cytokine signaling 3 is an inducible host factor that regulates virus egress during Ebola virus infection. / Okumura, Atsushi; Rasmussen, Angela L.; Halfmann, Peter; Feldmann, Friederike; Yoshimura, Akihiko; Feldmann, Heinz; Kawaoka, Yoshihiro; Harty, Ronald N.; Katze, Michael G.

In: Journal of Virology, Vol. 89, No. 20, 2015, p. 10399-10406.

Research output: Contribution to journalArticle

Okumura, A, Rasmussen, AL, Halfmann, P, Feldmann, F, Yoshimura, A, Feldmann, H, Kawaoka, Y, Harty, RN & Katze, MG 2015, 'Suppressor of cytokine signaling 3 is an inducible host factor that regulates virus egress during Ebola virus infection', Journal of Virology, vol. 89, no. 20, pp. 10399-10406. https://doi.org/10.1128/JVI.01736-15
Okumura, Atsushi ; Rasmussen, Angela L. ; Halfmann, Peter ; Feldmann, Friederike ; Yoshimura, Akihiko ; Feldmann, Heinz ; Kawaoka, Yoshihiro ; Harty, Ronald N. ; Katze, Michael G. / Suppressor of cytokine signaling 3 is an inducible host factor that regulates virus egress during Ebola virus infection. In: Journal of Virology. 2015 ; Vol. 89, No. 20. pp. 10399-10406.
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