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

研究成果: Article査読

26 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)10399-10406
ページ数8
ジャーナルJournal of Virology
89
20
DOI
出版ステータスPublished - 2015

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

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