DDX21 translocates from nucleus to cytoplasm and stimulates the innate immune response due to dengue virus infection

Dong, Yangchao; Ye, Wei; Yang, Jing; Han, Pei-jun; Wang, Yuan; Ye, Chuantao; Weng, Daihui; Zhang, Fanglin; Zhang, Xu; Lei, Yingfeng

doi:10.1016/j.bbrc.2016.03.120

Cited by 42 publications

(45 citation statements)

References 28 publications

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“…Similarly, NS2A and NS4B were shown to inhibit phosphorylation of TANK-binding kinase (TBK1) and its substrate IRF3 [70]. Another member of the DExD/H box helicases family that has a less clear role in innate immune response, DDX21, is a target of DENV NS2B/NS3 protease and its degradation was shown to facilitate DENV replication [71]. NS2B/NS3 also cleaves/inactivates STING, inhibiting the TBK1-mediated IFN expression [28,29].…”

Section: Evasion From Host Innate Immune Responsementioning

confidence: 99%

Non-Canonical Roles of Dengue Virus Non-Structural Proteins

Zeidler

Fernandes-Siqueira

Barbosa

et al. 2017

Viruses

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The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV) non-structural proteins (NSPs), which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection.

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Section: Evasion From Host Innate Immune Responsementioning

confidence: 99%

Non-Canonical Roles of Dengue Virus Non-Structural Proteins

Zeidler

Fernandes-Siqueira

Barbosa

et al. 2017

Viruses

View full text Add to dashboard Cite

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“…Other RNA-binding proteins have been implicated in the recognition or restriction of viral RNAs, suggesting that there are additional players to be discovered (Guo et al 2004;Miyashita et al 2011;Dong et al 2016).…”

mentioning

confidence: 99%

A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation

et al. 2016

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RNA degradation is tightly regulated to selectively target aberrant RNAs, including viral RNA, but this regulation is incompletely understood. Through RNAi screening in Drosophila cells, we identified the 3 ′ -to-5 ′ RNA exosome and two components of the exosome cofactor TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) complex, dMtr4 and dZcchc7, as antiviral against a panel of RNA viruses. We extended our studies to human orthologs and found that the exosome as well as TRAMP components hMTR4 and hZCCHC7 are antiviral. While hMTR4 and hZCCHC7 are normally nuclear, infection by cytoplasmic RNA viruses induces their export, forming a cytoplasmic complex that specifically recognizes and induces degradation of viral mRNAs. Furthermore, the 3 ′ untranslated region (UTR) of bunyaviral mRNA is sufficient to confer virus-induced exosomal degradation. Altogether, our results reveal that signals from viral infection repurpose TRAMP components to a cytoplasmic surveillance role where they selectively engage viral RNAs for degradation to restrict a broad range of viruses.

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“…Whether DDX21 can similarly impact the replication of other influenza viruses is still unknown. Furthermore, DDX21 translocates from nucleus to inhibit dengue virus replication in the early stages of the infection [64], participates in cellular defense against Hantaan virus [164] and regulates translation of polycistronic mRNA of Borna disease [62]. However, DDX21 also plays a role in HIV-1 pathogenesis by promoting Rev oligomerization on the Rev-responsive element, thus aiding the export of viral transcripts to cytosol [63].…”

Section: Ddx21mentioning

confidence: 99%