The VP35 protein of Ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide

• Published in: Journal of general virology 2010-02, Vol.91 (2), p.352-361
• Main Authors: Jin, Huali, Yan, Zhipeng, Prabhakar, Bellur S, Feng, Zongdi, Ma, Yijie, Verpooten, Dustin, Ganesh, Balaji, He, Bin
• Format: Article
• Language: English
• Subjects: Animal; Animals; Biological and medical sciences; Cells, Cultured; Cercopithecus aethiops; Cytokines - genetics; Cytokines - immunology; Dendritic Cells - immunology; Dendritic Cells - virology; Ebola virus; Ebolavirus - genetics; Ebolavirus - immunology; Fundamental and applied biological sciences. Psychology; Hemorrhagic Fever, Ebola - genetics; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - virology; Lipopolysaccharides - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Miscellaneous; T-Lymphocytes - immunology; Vero Cells; Viral Regulatory and Accessory Proteins - genetics; Viral Regulatory and Accessory Proteins - immunology; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.017343-0

Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612, USA Correspondence Bin He tshuo{at}uic.edu Ebola virus causes rapidly progressive haemorrhagic fever, which is associated with severe immuosuppression. In infected dendritic cells (DCs), 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 DCs. When expressed in mouse immature DCs, Ebola virus VP35 prevents virus-stimulated expression of CD40, CD80, CD86 and major histocompatibility complex class II. Further, it suppresses the induction of cytokines such as interleukin (IL)-6, IL-12, tumour necrosis factor and alpha/beta interferon (IFN- / β ). Notably, Ebola VP35 attenuates the ability of DCs to stimulate the activation of CD4 + T cells. Addition of type I IFN 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 abolishes its activity, whereas a mutation in the RNA binding motif has no effect. Our work highlights a critical role of VP35 in viral interference in DC function with resultant deficiency in T-cell function, which may contribute to the profound virulence of Ebola virus infection. These authors contributed equally to this work.