Dengue virus targets the adaptor protein MITA to subvert host innate immunity.

Dengue is one of the most important arboviral diseases caused by infection of four serotypes of dengue virus (DEN). We found that activation of interferon regulatory factor 3 (IRF3) triggered by viral infection and by foreign DNA and RNA stimulation was blocked by DEN-encoded NS2B3 through a proteas...

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Autores principales:	Chia-Yi Yu, Tsung-Hsien Chang, Jian-Jong Liang, Ruei-Lin Chiang, Yi-Ling Lee, Ching-Len Liao, Yi-Ling Lin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/11abf349e5af46ddb7c9fe19efa607d3
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spelling	oai:doaj.org-article:11abf349e5af46ddb7c9fe19efa607d32021-11-18T06:04:15ZDengue virus targets the adaptor protein MITA to subvert host innate immunity.1553-73661553-737410.1371/journal.ppat.1002780https://doaj.org/article/11abf349e5af46ddb7c9fe19efa607d32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761576/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Dengue is one of the most important arboviral diseases caused by infection of four serotypes of dengue virus (DEN). We found that activation of interferon regulatory factor 3 (IRF3) triggered by viral infection and by foreign DNA and RNA stimulation was blocked by DEN-encoded NS2B3 through a protease-dependent mechanism. The key adaptor protein in type I interferon pathway, human mediator of IRF3 activation (MITA) but not the murine homologue MPYS, was cleaved in cells infected with DEN-1 or DEN-2 and with expression of the enzymatically active protease NS2B3. The cleavage site of MITA was mapped to LRR↓(96)G and the function of MITA was suppressed by dengue protease. DEN replication was reduced with overexpression of MPYS but not with MITA, while DEN replication was enhanced by MPYS knockdown, indicating an antiviral role of MITA/MPYS against DEN infection. The involvement of MITA in DEN-triggered innate immune response was evidenced by reduction of IRF3 activation and IFN induction in cells with MITA knockdown upon DEN-2 infection. NS2B3 physically interacted with MITA, and the interaction and cleavage of MITA could be further enhanced by poly(dA:dT) stimulation. Thus, we identified MITA as a novel host target of DEN protease and provide the molecular mechanism of how DEN subverts the host innate immunity.Chia-Yi YuTsung-Hsien ChangJian-Jong LiangRuei-Lin ChiangYi-Ling LeeChing-Len LiaoYi-Ling LinPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002780 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Chia-Yi Yu Tsung-Hsien Chang Jian-Jong Liang Ruei-Lin Chiang Yi-Ling Lee Ching-Len Liao Yi-Ling Lin Dengue virus targets the adaptor protein MITA to subvert host innate immunity.
description	Dengue is one of the most important arboviral diseases caused by infection of four serotypes of dengue virus (DEN). We found that activation of interferon regulatory factor 3 (IRF3) triggered by viral infection and by foreign DNA and RNA stimulation was blocked by DEN-encoded NS2B3 through a protease-dependent mechanism. The key adaptor protein in type I interferon pathway, human mediator of IRF3 activation (MITA) but not the murine homologue MPYS, was cleaved in cells infected with DEN-1 or DEN-2 and with expression of the enzymatically active protease NS2B3. The cleavage site of MITA was mapped to LRR↓(96)G and the function of MITA was suppressed by dengue protease. DEN replication was reduced with overexpression of MPYS but not with MITA, while DEN replication was enhanced by MPYS knockdown, indicating an antiviral role of MITA/MPYS against DEN infection. The involvement of MITA in DEN-triggered innate immune response was evidenced by reduction of IRF3 activation and IFN induction in cells with MITA knockdown upon DEN-2 infection. NS2B3 physically interacted with MITA, and the interaction and cleavage of MITA could be further enhanced by poly(dA:dT) stimulation. Thus, we identified MITA as a novel host target of DEN protease and provide the molecular mechanism of how DEN subverts the host innate immunity.
format	article
author	Chia-Yi Yu Tsung-Hsien Chang Jian-Jong Liang Ruei-Lin Chiang Yi-Ling Lee Ching-Len Liao Yi-Ling Lin
author_facet	Chia-Yi Yu Tsung-Hsien Chang Jian-Jong Liang Ruei-Lin Chiang Yi-Ling Lee Ching-Len Liao Yi-Ling Lin
author_sort	Chia-Yi Yu
title	Dengue virus targets the adaptor protein MITA to subvert host innate immunity.
title_short	Dengue virus targets the adaptor protein MITA to subvert host innate immunity.
title_full	Dengue virus targets the adaptor protein MITA to subvert host innate immunity.
title_fullStr	Dengue virus targets the adaptor protein MITA to subvert host innate immunity.
title_full_unstemmed	Dengue virus targets the adaptor protein MITA to subvert host innate immunity.
title_sort	dengue virus targets the adaptor protein mita to subvert host innate immunity.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/11abf349e5af46ddb7c9fe19efa607d3
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Dengue virus targets the adaptor protein MITA to subvert host innate immunity.

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