PMID:19828757

Citation	Jin, H, Yan, Z, Prabhakar, BS, Feng, Z, Ma, Y, Verpooten, D, Ganesh, B and He, B (2010) The VP35 protein of Ebola virus impairs dendritic cell maturation induced by virus and lipopolysaccharide. J. Gen. Virol. 91:352-61
Abstract	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 alpha and alpha/beta interferon (IFN-alpha/beta). 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.
Links	PubMed PMC2831215 Online version:10.1099/vir.0.017343-0
Keywords	Animals; Cells, Cultured; Cercopithecus aethiops; Cytokines/genetics; Cytokines/immunology; Dendritic Cells/immunology; Dendritic Cells/virology; Ebolavirus/genetics; Ebolavirus/immunology; Hemorrhagic Fever, Ebola/genetics; Hemorrhagic Fever, Ebola/immunology; Hemorrhagic Fever, Ebola/virology; Lipopolysaccharides/immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes/immunology; Vero Cells; Viral Regulatory and Accessory Proteins/genetics; Viral Regulatory and Accessory Proteins/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
EBOZM:VP35	involved_in	GO:0039505: suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
EBOZM:VP35	involved_in	GO:0030683: evasion or tolerance by virus of host immune response	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
EBOZM:VP35		GO:0046775: suppression by virus of host cytokine production	ECO:0000314:		P		Fig. 3 and Figs. 6DEF	complete CACAO 2409
EBOZM:VP35		GO:0039505: suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II	ECO:0000315:		P		Fig. 2 and Fig. 4	complete CACAO 2410
EBOZM:VP35		GO:0050868: negative regulation of T cell activation	ECO:0000315:		P		Fig. 5	complete CACAO 2411
EBOZM:VP35		GO:0030683: evasion or tolerance by virus of host immune response	ECO:0000314:		P		Fig. 6 Inhibits dendritic cell maturation	complete CACAO 2412
EBOZM:VP35	involved_in	GO:0046775: suppression by virus of host cytokine production	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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