Cutting Edge: Oseltamivir decreases T cell GM1 expression and inhibits clearance of respiratory syncytial virus: potential role of endogenous sialidase in antiviral immunity.
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.
Moore
Martin L
ML
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Chi
Michael H
MH
Zhou
Weisong
W
Goleniewska
Kasia
K
O'Neal
Jamye F
JF
Higginbotham
James N
JN
Peebles
R Stokes
RS
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
D000998:Antiviral Agents; D053139:Oseltamivir; D005677:G(M1) Ganglioside; D009439:Neuraminidase