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CD8-Mediated Protection against Ebola Virus Infection Is Perforin Dependent

Manisha Gupta^1,*, Patricia Greer, Siddhartha Mahanty^2,*, Wun-Ju Shieh, Sherif R. Zaki, Rafi Ahmed and Pierre E. Rollin^*

^* Special Pathogens Branch and Infectious Diseases Pathology Activity, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; and Emory Vaccine Research Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322

CD8 T cells have been shown to play an important role in the clearance and protection against fatal Ebola virus infection. In this study, we examined the mechanisms by which CD8 T cells mediate this protection. Our data demonstrate that all normal mice infected s.c. with a mouse-adapted Ebola virus survived the infection, as did 100% of mice deficient in Fas and 90% of those deficient in IFN-. In contrast, perforin-deficient mice uniformly died after s.c. challenge. Perforin-deficient mice failed to clear viral infection even though they developed normal levels of neutralizing anti-Ebola Abs and 5- to 10-fold higher levels of IFN- than control mice. Using MHC class I tetramers, we have also shown that perforin-deficient mice have 2- to 4-fold higher numbers of Ebola-specific CD8s than control mice. These findings suggest that the clearance of Ebola virus is perforin-dependent and provide an additional example showing that this basic immunologic mechanism is not limited to the clearance of noncytopathic viruses.

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