LIGHT induces distinct signals to clear an AAVexpressed persistent antigen in the mouse liver and to induce liver inflammation

Michael L. Washburn, Grigoriy I. Kovalev, Ekaterina Koroleva, Yang Xin Fu, Lishan Su

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Infection with adeno-associated virus (AAV) vector with liver tropism leads to persistent expression of foreign antigens in the mouse liver, with no significant liver inflammation or pathology. This provides a model to investigate antigen persistence in the liver and strategies to modulate host immunity to reduce or clear the foreign antigen expressed from AAV vector in the liver. Methods/Principal Findings: We showed that expressing LIGHT with an adenovirus vector (Ad) in mice with established AAV in the liver led to clearance of the AAV. Ad-LIGHT enhanced CD8 effector T cells in the liver, correlated with liver inflammation. LTbR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. Conclusions/Significance: Our data suggest that LIGHT interaction with the LTbR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immunotherapeutics in treating people chronically infected with hepato-tropic viruses.

Original languageEnglish (US)
Article numbere10585
JournalPLoS One
Volume5
Issue number5
DOIs
StatePublished - Sep 17 2010

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Dependovirus
Liver
Viruses
inflammation
Inflammation
antigens
Light
Antigens
liver
mice
Tropics
tropisms
Tropism
T-cells
Adenoviridae
Pathology
Immunity
tropics
T-lymphocytes
immunity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

LIGHT induces distinct signals to clear an AAVexpressed persistent antigen in the mouse liver and to induce liver inflammation. / Washburn, Michael L.; Kovalev, Grigoriy I.; Koroleva, Ekaterina; Fu, Yang Xin; Su, Lishan.

In: PLoS One, Vol. 5, No. 5, e10585, 17.09.2010.

Research output: Contribution to journalArticle

Washburn, Michael L. ; Kovalev, Grigoriy I. ; Koroleva, Ekaterina ; Fu, Yang Xin ; Su, Lishan. / LIGHT induces distinct signals to clear an AAVexpressed persistent antigen in the mouse liver and to induce liver inflammation. In: PLoS One. 2010 ; Vol. 5, No. 5.
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