Subversion of interferon by dengue virus.
Dengue virus is sensed in mammalian cells by Toll-like receptors and DExD/H box RNA helicases, triggering a Type 1 interferon response. Interferon acts upon infected and noninfected cells by stimulating the JAK/STAT signaling pathway resulting in the activation of interferon stimulated genes that lead cells toward the establishment of an antiviral response. The recognition of the importance of this rapid protective response should come with the realization that dengue virus would circumvent the interferon response to propagate in the host. There is recent, mounting evidence for mechanisms encoded by the dengue virus that weaken interferon signaling. Nonstructural proteins expressed separately or in replicon vectors block phosphorylation and down-regulate expression of major components of the JAK/STAT pathway, causing reduced activation of gene expression in response to IFNalpha/beta interferon. As our understanding of viral-host interaction increases, opportunities for improved biological models and therapeutics discovery arise.
Muñoz-Jordán
Jorge L
JL
Division of Vector Borne Infectious Diseases, Dengue Branch, Centers for Disease Control and Prevention, 1324 Calle Cañada, San Juan, PR 00920, USA. ckq2@cdc.gov
D003715:Dengue / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D015536:Down-Regulation; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D053612:Janus Kinases / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication
D016898:Interferon-alpha; D050791:STAT Transcription Factors; D016899:Interferon-beta; D053612:Janus Kinases