Murine gamma-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus-induced vascular disease.
Fundamental issues remain unresolved regarding the possible contribution of viruses to vascular pathology, as well as the role of the immune system in regulating these processes. Here we demonstrate that infection of mice with gamma-herpesvirus 68 (gammaHV68) provides a novel model for addressing these issues. Interferon-gamma receptor-deficient (IFNgammaR-/-) mice died weeks to months after gammaHV68 infection from a severe large-vessel panarteritis. GammaHV68-infected B cell-deficient and normal weanling mice exhibited milder large-vessel arteritis. Immunohistochemical analyses demonstrated gammaHV68 antigen in arteritic lesions and revealed a striking tropism of gammaHV68 for smooth muscle cells. These studies demonstrate that IFN-gamma is essential for control of chronic vascular pathology induced by gammaHV68 and suggest gamma-herpesviruses as candidate etiologic agents for human vasculitis.
Weck
K E
KE
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dal Canto
A J
AJ
Gould
J D
JD
O'Guin
A K
AK
Roth
K A
KA
Saffitz
J E
JE
Speck
S H
SH
Virgin
H W
HW
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001167:Arteritis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D004195:Disease Models, Animal; D018142:Gammaherpesvirinae / Q000276:immunology / Q000502:physiology*; D017353:Gene Deletion; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000096743:Interferon gamma Receptor
D000956:Antigens, Viral; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor