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Cutting Edge: Oseltamivir Decreases T Cell GM1 Expression and Inhibits Clearance of Respiratory Syncytial Virus: Potential Role of Endogenous Sialidase in Antiviral Immunity¹

Martin L. Moore^*, Michael H. Chi^*, Weisong Zhou^*, Kasia Goleniewska^*, Jamye F. O’Neal^*, James N. Higginbotham and R. Stokes Peebles, Jr.^2,*

^* Department of Medicine and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HL069949, AI054660, and T32 GM07569, and American Academy of Allergy, Asthma, and Immunology Education and Research Trust Award.

² Address correspondence and reprint requests to Dr. R. Stokes Peebles, Jr., T-1218 MCN, Vanderbilt University Medical Center, Nashville, TN 37232-2650. E-mail address: stokes.peebles{at}vanderbilt.edu

³ Abbreviations used in this paper: GSL, glycosphingolipid; RSV, respiratory syncytial virus; NA, neuraminidase; CtxB, cholera toxin B subunit; 4-MUNANA, 2'-(4-methylumbelliferyl)--D-N-acetylneuraminic acid; 4-MU, 4-methylumbelliferone; d.p.i., day postinfection; MFI, mean fluorescence intensity.

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