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.
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: T A Endo; M Masuhara; M Yokouchi; R Suzuki; H Sakamoto; K Mitsui; A Matsumoto; S Tanimura; M Ohtsubo; H Misawa; T Miyazaki; N Leonor; T Taniguchi; T Fujita; Y Kanakura; S Komiya; A Yoshimura Journal: Nature Date: 1997-06-26 Impact factor: 49.962
Authors: R Starr; T A Willson; E M Viney; L J Murray; J R Rayner; B J Jenkins; T J Gonda; W S Alexander; D Metcalf; N A Nicola; D J Hilton Journal: Nature Date: 1997-06-26 Impact factor: 49.962
Authors: Wendy Peters; Jason G Cyster; Matthias Mack; Detlef Schlöndorff; Andrea J Wolf; Joel D Ernst; Israel F Charo Journal: J Immunol Date: 2004-06-15 Impact factor: 5.422
Authors: Lukasz Kedzierski; E Bridie Clemens; Nicola L Bird; Benjamin T Kile; Gabrielle T Belz; Nicos A Nicola; Katherine Kedzierska; Sandra E Nicholson Journal: Immunol Cell Biol Date: 2015-06-16 Impact factor: 5.126
Authors: Boris M Hartmann; Juilee Thakar; Randy A Albrecht; Stefan Avey; Elena Zaslavsky; Nada Marjanovic; Maria Chikina; Miguel Fribourg; Fernand Hayot; Mirco Schmolke; Hailong Meng; James Wetmur; Adolfo García-Sastre; Steven H Kleinstein; Stuart C Sealfon Journal: J Virol Date: 2015-07-29 Impact factor: 5.103
Authors: Lukasz Kedzierski; Edmond M Linossi; Tatiana B Kolesnik; E Bridie Day; Nicola L Bird; Benjamin T Kile; Gabrielle T Belz; Donald Metcalf; Nicos A Nicola; Katherine Kedzierska; Sandra E Nicholson Journal: PLoS Pathog Date: 2014-05-08 Impact factor: 6.823