title: Caveolin-1 limits human influenza A virus (H1N1) propagation in mouse embryo-derived fibroblasts.
abstract: Caveolin expression supports the multiplication of retro-, ortho- and paramyxoviruses in susceptible cells. However, human influenza A virus (IAV), an orthomyxovirus, does not multiply efficiently in mouse embryo fibroblasts (MEFs), which are abundant in caveolin-1 (Cav-1). Surprisingly, the absence of Cav-1 in a MEF cell line removed the block for IAV replication and raised the infectious titer 250-fold, whereas the re-introduction of Cav-1 reversed the effect. The monitoring of cellular pathways revealed that Cav-1 loss considerably increased activities of p53. Furthermore, infection of MEF Cav-1 (-/-) induced reactive oxygen species (ROS) and pronounced apoptosis in the late phase of viral multiplication, but no type I IFN response. Strikingly, pharmacological inactivation showed that the elevated levels of ROS together with apoptosis caused the increase of virus yield. Thus, Cav-1 represents a new negative regulator of IAV infection in MEF that diminishes IAV infectious titer by controlling virus-supportive pathways.
authors.affiliation: Department of Gene Regulation and Differentiation, Helmholtz Center for Infection Research, D-38124 Braunschweig, Germany. Electronic address: KBO13@helmholtz-hzi.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Bohm
authors.affiliation: Department of Gene Regulation and Differentiation, Helmholtz Center for Infection Research, D-38124 Braunschweig, Germany. Electronic address: ljsun@home.ipe.ac.cn.
authors.forename: Lijing
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Gene Regulation and Differentiation, Helmholtz Center for Infection Research, D-38124 Braunschweig, Germany. Electronic address: DTH10@helmholtz-hzi.de.
authors.forename: Divyeshsinh
authors.initials: D
authors.lastname: Thakor
authors.affiliation: Department of Gene Regulation and Differentiation, Helmholtz Center for Infection Research, D-38124 Braunschweig, Germany. Electronic address: MWI@helmholtz-hzi.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wirth
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000821:virology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014779:Virus Replication
chemical_list: D051242:Caveolin 1
keywords: Apoptosis; Caveolin-1-deficiency; Human influenza A virus; Mouse embryo-derived fibroblasts; Reactive oxygen species; Reporter gene array; Restriction