4.6 Article

Cutting edge: Oseltamivir decreases T cell GM1 expression and inhibits clearance of respiratory syncytial virus: Potential role of endogenous sialidase in antiviral immunity

Journal

JOURNAL OF IMMUNOLOGY
Volume 178, Issue 5, Pages 2651-2654

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.5.2651

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Funding

  1. NHLBI NIH HHS [HL 069949] Funding Source: Medline
  2. NIAID NIH HHS [AI 054660] Funding Source: Medline
  3. NIGMS NIH HHS [T32 GM 07569] Funding Source: Medline

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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 hings 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 antiviralimmunity. Also, oseltamivir, an important anti influenza drug, inhibits the clearance of a respiratory virus that lacks a neuranzinidase gene, RSV.

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