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oai:riubu.ubu.es:10259/83722024-01-18T01:05:19Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Rodríguez Madoz, Juan R. c613bd1a-30c8-4c5b-b374-a38da4826c29 600 Belicha Villanueva, Alan 86accf09-17b2-4fee-9b4b-ad0456316daa 600 Bernal Rubio, Dabeiba 0b48dbd4-a9f2-4ee4-be8d-a9de357a0f92 600 Ashour, Joseph 4edd224f-2c6f-41fb-a5e9-dee2fe3fb8e0 600 Ayllón Barasoain, Juan 852 600 0000-0002-7556-8106 Fernández Sesma, Ana b3231b3c-69c4-4f94-95d6-3802b2e0925c 600 2024-01-17T12:29:52Z 2024-01-17T12:29:52Z 2010-10 0022-538X http://hdl.handle.net/10259/8372 10.1128/jvi.01051-10 1098-5514 Dengue virus (DENV) is the most prevalent arthropod-borne human virus, able to infect and replicate in human dendritic cells (DCs), inducing their activation and the production of proinflammatory cytokines. However, DENV can successfully evade the immune response in order to produce disease in humans. Several mechanisms of immune evasion have been suggested for DENV, most of them involving interference with type I interferon (IFN) signaling. We recently reported that DENV infection of human DCs does not induce type I IFN production by those infected DCs, impairing their ability to prime naive T cells toward Th1 immunity. In this article, we report that DENV also reduces the ability of DCs to produce type I IFN in response to several inducers, such as infection with other viruses or exposure to Toll-like receptor (TLR) ligands, indicating that DENV antagonizes the type I IFN production pathway in human DCs. DENV-infected human DCs showed a reduced type I IFN response to Newcastle disease virus (NDV), Sendai virus (SeV), and Semliki Forest virus (SFV) infection and to the TLR3 agonist poly(I:C). This inhibitory effect is DENV dose dependent, requires DENV replication, and takes place in DENV-infected DCs as early as 2 h after infection. Expressing individual proteins of DENV in the presence of an IFN-α/β production inducer reveals that a catalytically active viral protease complex is required to reduce type I IFN production significantly. These results provide a new mechanism by which DENV evades the immune system in humans. This work was funded by 1R01AI073450 (to A.F.-S.) and a Ramon Areces Foundation Fellowship (to J.R.R.-M.). J.R.R.-M. designed and performed experiments, analyzed data, and wrote the manuscript. A.B.-V. and D.B.-R. performed experiments. J. Ashour and J. Ayllon provided reagents. A.F.-S. designed experiments, analyzed data, wrote the manuscript, and supervised the project. application/pdf eng American Society for Microbiology Journal of Virology. 2010, V. 84, n. 19, p. 9760-9774 https://doi.org/10.1128/jvi.01051-10 Salud Enfermedades infecciosas Medicina Health Communicable diseases Medicine Inhibition of the Type I Interferon Response in Human Dendritic Cells by Dengue Virus Infection Requires a Catalytically Active NS2B3 Complex info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/openAccess Journal of Virology 84 19 9760 9774 THUMBNAIL Rodríguez-jv_2010.pdf.jpg Rodríguez-jv_2010.pdf.jpg IM Thumbnail image/jpeg 4706 https://riubu.ubu.es/bitstream/10259/8372/3/Rodr%c3%adguez-jv_2010.pdf.jpg 910dc7f45231e7af6667c0acff3b2bbe MD5 3 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/8372/2/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 2 ORIGINAL Rodríguez-jv_2010.pdf Rodríguez-jv_2010.pdf application/pdf 2450582 https://riubu.ubu.es/bitstream/10259/8372/1/Rodr%c3%adguez-jv_2010.pdf 06d55b05754a0df79dc0819bbb53a684 MD5 1 10259/8372 oai:riubu.ubu.es:10259/8372 2024-01-18 02:05:19.744 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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