LIGHT induces distinct signals to clear an AAV-expressed persistent antigen in the mouse liver and to induce liver inflammation.
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.


RESULTS
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. LTbetaR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbetaR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation.


CONCLUSIONS
Our data suggest that LIGHT interaction with the LTbetaR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immuno-therapeutics in treating people chronically infected with hepato-tropic viruses.
Washburn
Michael L
ML
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Kovalev
Grigoriy I
GI
Koroleva
Ekaterina
E
Fu
Yang-Xin
YX
Su
Lishan
L
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D000229:Dependovirus / Q000235:genetics / Q000276:immunology*; D016679:Genome, Viral / Q000235:genetics; D007249:Inflammation / Q000473:pathology / Q000821:virology*; D008099:Liver / Q000473:pathology* / Q000821:virology*; D053259:Lymphotoxin beta Receptor / Q000172:deficiency; D051379:Mice; D010322:Parvoviridae Infections / Q000473:pathology / Q000821:virology; D015398:Signal Transduction / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*
D000956:Antigens, Viral; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14