title: Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages.
abstract: BACKGROUND
  Infection with pandemic (pdm) A/H1N1 virus induces high levels of pro-inflammatory mediators in blood and lungs of experimental animals and humans.
  
  
  METHODS
  To compare the involvement of seasonal A/PR/8/34 and pdm A/H1N1 virus strains in the regulation of inflammatory responses, we analyzed the changes in the whole-genome expression induced by these strains in macrophages and A549 epithelial cells. We also focused on the functional implications (cytokine production) of the differential induction of suppressors of cytokine signaling (SOCS)-1, SOCS-3, retinoid-inducible gene (RIG)-I and interferon receptor 1 (IFNAR1) genes by these viral strains in early stages of the infection.
  
  
  RESULTS
  We identified 130 genes differentially expressed by pdm A/H1N1 and A/PR/8/34 infections in macrophages. mRNA levels of SOCS-1 and RIG-I were up-regulated in macrophages infected with the A/PR/8/34 but not with pdm A/H1N1 virus. mRNA levels of SOCS-3 and IFNAR1 induced by A/PR/8/34 and pdm A/H1N1 strains in macrophages, as well as in A549 cells were similar. We found higher levels of IL-6, TNF-α, IL-10, CCL3, CCL5, CCL4 and CXCL8 (p < 0.05) in supernatants from cultures of macrophages infected with the pdm A/H1N1 virus compared to those infected with the A/PR/8/34 strain, coincident with the lack of SOCS-1 and RIG-I expression. In contrast, levels of INF-α were higher in cultures of macrophages 48h after infection with the A/PR/8/34 strain than with the pdm A/H1N1 virus.
  
  
  CONCLUSIONS
  These findings suggest that factors inherent to the pdm A/H1N1 viral strain may increase the production of inflammatory mediators by inhibiting SOCS-1 and modifying the expression of antiviral immunity-related genes, including RIG-I, in human macrophages.
authors: Department of Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
authors: Gustavo
authors: G
authors: Ramírez-Martínez
authors: Alfredo
authors: A
authors: Cruz-Lagunas
authors: Luis
authors: L
authors: Jiménez-Alvarez
authors: Enrique
authors: E
authors: Espinosa
authors: Blanca
authors: B
authors: Ortíz-Quintero
authors: Teresa
authors: T
authors: Santos-Mendoza
authors: María Teresa
authors: MT
authors: Herrera
authors: Elsy
authors: E
authors: Canché-Pool
authors: Criselda
authors: C
authors: Mendoza
authors: José L
authors: JL
authors: Bañales
authors: Sara A
authors: SA
authors: García-Moreno
authors: Juan
authors: J
authors: Morán
authors: Carlos
authors: C
authors: Cabello
authors: Lorena
authors: L
authors: Orozco
authors: Irma
authors: I
authors: Aguilar-Delfín
authors: Alfredo
authors: A
authors: Hidalgo-Miranda
authors: Sandra
authors: S
authors: Romero
authors: Benjamin T
authors: BT
authors: Suratt
authors: Moisés
authors: M
authors: Selman
authors: Joaquín
authors: J
authors: Zúñiga
mesh_terms: D018925:Chemokines / Q000096:biosynthesis*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007109:Immunity / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D058873:Pandemics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D012621:Seasons; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018925:Chemokines; C507964:IFNAR1 protein, human; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053633:Receptor, Interferon alpha-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases