Inhibition of interferon signaling by dengue virus
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TLDR
It is found that expression in human A549 cells of the dengue virus nonstructural proteins NS2A, NS4A, or NS4B enhances replication of an IFN-sensitive virus.Abstract:
Dengue virus is a worldwide-distributed mosquito-borne flavivirus with a positive strand RNA genome. Its transcribed polyprotein is cleaved by host- and virus-encoded peptidases into 10 proteins, some of which are of unknown function. Although dengue virus-infected cells seem to be resistant to the antiviral action of IFN, the viral products that mediate this resistance are unknown. Therefore, we have analyzed the ability of the 10 dengue virus-encoded proteins to antagonize the IFN response. We found that expression in human A549 cells of the dengue virus nonstructural proteins NS2A, NS4A, or NS4B enhances replication of an IFN-sensitive virus. Moreover, expression of NS4B and, to a lesser extent, of NS2A and NS4A proteins results in down-regulation of IFN-β-stimulated gene expression. Cells expressing NS4B or infected with dengue virus do not exhibit nuclear signal transducer and activator of transcription (STAT) 1 on treatment with IFN-β or IFN-γ, indicating that NS4B might be involved in blocking IFN signaling during dengue virus infections. This protein, encoded by a positive strand RNA virus, is implicated as an IFN-signaling inhibitor.read more
Citations
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Flaviviridae :T he Viruses and Their Replication
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Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.
TL;DR: Applied aspects that arise from an increase in knowledge in this area are described, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.
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Composition and three-dimensional architecture of the dengue virus replication and assembly sites.
Sonja Welsch,Sven Miller,Inés Romero-Brey,Andreas Merz,Christopher K. E. Bleck,Paul Walther,Stephen D. Fuller,Claude Antony,Jacomine Krijnse-Locker,Ralf Bartenschlager +9 more
TL;DR: Dengue virus (DENV) modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus, which could explain the coordination of distinct steps of the flavivirus replication cycle.
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The interferon response circuit: Induction and suppression by pathogenic viruses
TL;DR: The current view on the balancing act between virus-induced IFN responses and the viral counterplayers is discussed.
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Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling
Alesha Grant,Sanket S. Ponia,Shashank Tripathi,Vinod Balasubramaniam,Lisa Miorin,Marion Sourisseau,Megan C. Schwarz,Mari Paz Sánchez-Seco,Matthew J. Evans,Sonja M. Best,Adolfo García-Sastre +10 more
TL;DR: It is reported that the nonstructural protein NS5 of ZIKV and other flaviviruses examined could suppress IFN signaling, but through different mechanisms, although by virus-specific mechanisms.
References
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