Interferon-? Inhibits Ebola Virus Infection

Rhein, Bethany A.; Powers, Linda S.; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K.; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A.; Monick, Martha M.; Maury, Wendy

Macrophages and dendritic cells (DCs) play an important role in EBOV pathogenesis as sites of early and sustained virus replication [3, 4] . EBOV infection causes dysregulation of these antigen-presenting cells, increasing production and release of pro-inflammatory proteins, vasoactive molecules, and coagulation factors [5] [6] [7] . Pro-inflammatory molecules recruit other target cells to the site of infection, providing additional cells for virus infection and increasing circulation of inflammatory cells and proteins. This uncontrolled amplification of infection and cytokine production results in dysregulation of the inflammatory response, leading to the systemic spread of the virus, excessive cytokine accumulation and circulatory collapse observed in cases of fatal EBOV hemorrhagic fever in humans and non-human primates [3, 4, 6, 8] . Contributing to this amplifying dysregulation, EBOV sustains replication in macrophages and DCs by counteracting early innate immune responses, thereby decreasing effective host responses to the virus [5, 9] . These events in combination with decreased T cell numbers observed in EBOV-infected individuals [10] are thought to lead to poor adaptive immune responses to infection.