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The VP35 Protein of Ebola Virus Impairs Dendritic Cell Maturation Induced by Virus and Lipopolysaccharide

University of Illinois at Chicago

¹ E-mail: tshuo{at}uic.edu

Ebola virus causes rapidly progressive hemorrhagic fever, which is associated with severe immuosuppression. In infected dendritic cells (DC), Ebola virus replicates efficiently and inhibits DC maturation without inducing cytokine expression, leading to impaired T cell proliferation. However, the underlying mechanism remains unclear. In this study, we report that Ebola virus VP35 impairs the maturation of mouse dendritic cells. When expressed in mouse immature DCs, Ebola virus VP35 prevents virus-stimulated expression of CD40, CD80, CD86, and MHC class II. Further, it suppresses the induction of cytokines such as IL-6, IL-12, TNF-, and interferon /β. Notably, Ebola VP35 attenuates the ability of DCs to stimulate the activation of CD4+T cells. Addition of type I interferon to mouse DCs only partially reverses the inhibitory effects of VP35. Moreover, VP35 perturbs mouse DC functions induced by lipopolysaccharide, an agonist of Toll-like receptor 4. Deletion of the amino terminus abolished its activity whereas a mutation in the RNA binding motif has no effect. Our work highlights a critical role of VP35 in viral interference of DC function with resultant deficiency in T cell function, which may contribute to the profound virulence of Ebola virus infection.

Received 5 October 2009; accepted 13 October 2009.