title: Influenza virus neuraminidase activates latent transforming growth factor beta.
abstract: Transforming growth factor beta (TGF-beta) is a family of proteins secreted by virtually all cells in a biologically inactive form. TGF-beta levels increase during many pathophysiological situations, including viral infection. The mechanism for increased TGF-beta activity during viral infection is not understood. We observed an increase in active TGF-beta levels within 1 day in mice infected with influenza virus. Further studies showed that the neuraminidase glycoprotein of influenza A and B viruses directly activates latent TGF-beta in vitro. There are sufficient levels of TGF-beta activated by virus to induce apoptosis in cells. In addition, influenza virus-induced apoptosis is partially inhibited by TGF-beta-specific antibodies. These novel findings suggest a potential role for activation of TGF-beta during the host response to influenza virus infection, specifically apoptosis. This is the first report showing direct activation of latent TGF-beta by a viral protein.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA. CherryS@svm.vetmed.wisc.edu
authors.forename: S
authors.initials: S
authors.lastname: Schultz-Cherry
authors.forename: V S
authors.initials: VS
authors.lastname: Hinshaw
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000201:enzymology*; D009981:Influenza B virus / Q000201:enzymology*; D007251:Influenza, Human / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D009439:Neuraminidase