title: Upregulation of the Suppressors of Cytokine Signaling 1 and 3 Is Associated with Arrest of Phosphorylated-STAT1 Nuclear Importation and Reduced Innate Response in Denguevirus-Infected Macrophages.
abstract: To clarify whether the suppressors of cytokine signaling (SOCS) are associated with denguevirus (DENV) evasion of the antiviral response, we analyzed the expression kinetics of SOCS1 and SOCS3 and of the antiviral genes MxA and OAS during DENV infection of U937 macrophages that were or not treated with interferon (IFN)-α. DENV infection produced a viral titer three times higher in untreated than in IFN-α-treated cells (p < 0.001 at 72 h postinfection [p.i.]). Partial inhibition of DENV replication was associated with reduced expression of MxA and OAS antiviral genes as well as higher SOCS1 and SOCS3 expression in DENV-infected cells than in cells treated only with IFN-α. Complete loss of phosphorylated-signal transducer and activator of transcription (p-STAT)2 and reduced nuclear importation of p-STAT1 were observed in DENV-infected cells compared to IFN-α treatment that induced p-STAT1 and p-STAT2. Our data thus suggest that overexpression of SOCS1 and SOCS3 induced by DENV infection leads to impairment of antiviral response through the inhibition of STAT functionality.
authors.affiliation: 1 Laboratorio de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, HGZ5, Instituto Mexicano del Seguro Social , Metepec, Puebla, México .|2 Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla , Puebla, México .
authors.forename: Tania
authors.initials: T
authors.lastname: Estrada-Jiménez
authors.affiliation: 2 Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla , Puebla, México .
authors.forename: Lourdes
authors.initials: L
authors.lastname: Millán-Pérez Peña
authors.affiliation: 1 Laboratorio de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, HGZ5, Instituto Mexicano del Seguro Social , Metepec, Puebla, México .
authors.forename: Lilian
authors.initials: L
authors.lastname: Flores-Mendoza
authors.affiliation: 3 Departamento de Ciencias de la Salud, Universidad Popular Autónoma del Estado de Puebla , Puebla, México .
authors.forename: Virginia
authors.initials: V
authors.lastname: Sedeño-Monge
authors.affiliation: 1 Laboratorio de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, HGZ5, Instituto Mexicano del Seguro Social , Metepec, Puebla, México .
authors.forename: Gerardo
authors.initials: G
authors.lastname: Santos-López
authors.affiliation: 2 Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla , Puebla, México .
authors.forename: Nora
authors.initials: N
authors.lastname: Rosas-Murrieta
authors.affiliation: 2 Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla , Puebla, México .
authors.forename: Sandra
authors.initials: S
authors.lastname: Reyes-Carmona
authors.affiliation: 4 Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo A.C. , Hermosillo, Sonora, Mexico .
authors.forename: Eli
authors.initials: E
authors.lastname: Terán-Cabanillas
authors.affiliation: 4 Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo A.C. , Hermosillo, Sonora, Mexico .
authors.forename: Jesus
authors.initials: J
authors.lastname: Hernández
authors.affiliation: 2 Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla , Puebla, México .
authors.forename: Irma
authors.initials: I
authors.lastname: Herrera-Camacho
authors.affiliation: 1 Laboratorio de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, HGZ5, Instituto Mexicano del Seguro Social , Metepec, Puebla, México .
authors.forename: Verónica
authors.initials: V
authors.lastname: Vallejo-Ruiz
authors.affiliation: 1 Laboratorio de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, HGZ5, Instituto Mexicano del Seguro Social , Metepec, Puebla, México .
authors.forename: Julio
authors.initials: J
authors.lastname: Reyes-Leyva
mesh_terms: D002460:Cell Line; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*
chemical_list: C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein