Interferon-γ Inhibits Ebola Virus Infection

Interferon-γ Inhibits Ebola Virus Infection For years I’ve been telling students to forget about type II (gamma) interferon in terms of protecting against viruses – antiviral therapy is mostly down to type I (alpha/beta) interferon. Well not in the case of Ebola virus seemingly.

With no current approved filovirus therapeutics, the recent Ebola virus epidemic in Guinea, Sierra Leone and Liberia emphasizes the need for effective treatments against this highly pathogenic family of viruses. The use of this drug to inhibit Ebola virus infection would allow rapid implementation of a novel antiviral therapy for future crises. Interferon gamma elicits an antiviral state in antigen-presenting cells and stimulates cellular immune responses. This paper demonstrates that interferon gamma profoundly inhibits Ebola virus infection of macrophages, which are early cellular targets of Ebola virus and identifies novel interferon gamma-stimulated genes in human macrophage populations that have not been previously appreciated to inhibit filoviruses or other negative strand RNA viruses. It also shows that interferon gamma given 24 hours prior to or after virus infection protects mice from lethal Ebola virus challenge, suggesting that this drug may serve as an effective prophylactic and/or therapeutic strategy against this deadly virus.

 

Interferon-γ Inhibits Ebola Virus Infection. (2015) PLoS Pathog 11(11): e1005263. doi:10.1371/journal.ppat.1005263
Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

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2 Responses to Interferon-γ Inhibits Ebola Virus Infection

  1. Roberta Ross says:

    Absolutely agreed!

  2. Chris Upton says:

    Poxvirus make an interferon-gamma binding protein to block it. In fact, myxoma virus infected cells secrete a bucket-load of this protein.

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