Inhibition of interferon signaling by dengue virus.
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-beta-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-beta or IFN-gamma, 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.
Muñoz-Jordan
Jorge L
JL
Department of Microbiology, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029.
Sánchez-Burgos
Gilma G
GG
Laurent-Rolle
Maudry
M
García-Sastre
Adolfo
A
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000502:physiology*; D010766:Phosphorylation; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; D007371:Interferon-gamma; D007372:Interferons