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: Martin L Moore, Michael H Chi, Weisong Zhou, Kasia Goleniewska, Jamye F O'Neal, James N Higginbotham, R Stokes Peebles Jr
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 5 Pg. 2651-4 (Mar 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17312105 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Oseltamivir
• G(M1) Ganglioside
• Neuraminidase

Topics

• Animals
• Antiviral Agents (pharmacology)
• CD8-Positive T-Lymphocytes (enzymology, immunology)
• Down-Regulation (drug effects, immunology)
• Female
• G(M1) Ganglioside (biosynthesis, immunology)
• Immunity, Cellular (drug effects, immunology)
• Lymphocyte Activation (drug effects)
• Membrane Microdomains (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Neuraminidase (antagonists & inhibitors, immunology)
• Oseltamivir (pharmacology)
• Respiratory Syncytial Virus Infections (immunology, metabolism)
• Respiratory Syncytial Viruses (immunology)
• Signal Transduction (drug effects, immunology)