title: Cutting Edge: Oseltamivir decreases T cell GM1 expression and inhibits clearance of respiratory syncytial virus: potential role of endogenous sialidase in antiviral immunity.
abstract: The sialoglycosphingolipid GM1 is important for lipid rafts and immune cell signaling. T cell activation in vitro increases GM1 expression and increases endogenous sialidase activity. GM1 expression has been hypothesized to be regulated by endogenous sialidase. We tested this hypothesis in vivo using a mouse model of respiratory syncytial virus (RSV) infection. RSV infection increased endogenous sialidase activity in lung mononuclear cells. RSV infection increased lung CD8+ T cell surface GM1 expression. Activated CD8+ T cells in the lungs of RSV-infected mice were GM1(high). Treatment of RSV-infected mice with the sialidase/neuraminidase inhibitor oseltamivir decreased T cell surface GM1 levels. Oseltamivir treatment decreased RSV-induced weight loss and inhibited RSV clearance. Our data indicate a novel role for an endogenous sialidase in regulating T cell GM1 expression and antiviral immunity. Also, oseltamivir, an important anti-influenza drug, inhibits the clearance of a respiratory virus that lacks a neuraminidase gene, RSV.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.forename: Michael H
authors.initials: MH
authors.lastname: Chi
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Jamye F
authors.initials: JF
authors.lastname: O'Neal
authors.forename: James N
authors.initials: JN
authors.lastname: Higginbotham
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005677:G(M1) Ganglioside / Q000096:biosynthesis / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000276:immunology; D053139:Oseltamivir / Q000494:pharmacology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D005677:G(M1) Ganglioside; D009439:Neuraminidase