INFLUENZA-VIRUS NEURAMINIDASE ACTIVATES LATENT TRANSFORMING GROWTH-FACTOR-BETA

Transforming growth factor beta (TGF-beta) is a family of proteins sec reted 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 T GF-beta levels within 1 day in mice infected with influenza virus, Fur ther 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 i n cells. In addition, influenza virus-induced apoptosis is partially i nhibited 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 firs t report showing direct activation of latent: TGF-beta by a viral prot ein.