Role of natural killer cells innate protection against lethal Ebola virus infection

Kelly L. Warfield, Jeremy G. Perkins, Dana L. Swenson, Emily M. Deal, Catharine M. Bosio, M. Javad Aman, Wayne M. Yokoyama, Howard A. Young, Sina Bavari

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1-3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell-mediated protection clearly depended on perforin, but not interferon-γ secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.

Original languageEnglish
Pages (from-to)169-179
Number of pages11
JournalJournal of Experimental Medicine
Volume200
Issue number2
DOIs
StatePublished - Jul 19 2004

Keywords

  • Filoviruses
  • Glycoprotein
  • Immunity
  • Matrix protein
  • Virus-like particles

Fingerprint Dive into the research topics of 'Role of natural killer cells innate protection against lethal Ebola virus infection'. Together they form a unique fingerprint.

  • Cite this

    Warfield, K. L., Perkins, J. G., Swenson, D. L., Deal, E. M., Bosio, C. M., Aman, M. J., Yokoyama, W. M., Young, H. A., & Bavari, S. (2004). Role of natural killer cells innate protection against lethal Ebola virus infection. Journal of Experimental Medicine, 200(2), 169-179. https://doi.org/10.1084/jem.20032141