Murine cytomegalovirus induces a Sjögren's syndrome-like disease in C57Bl/6-lpr/lpr mice.
OBJECTIVE
To analyze Fas and tumor necrosis factor receptor I (TNFRI) apoptosis pathways in salivary gland inflammatory disease induced by murine cytomegalovirus (MCMV) infection.


METHODS
Four different strains of mice (C57BI/6 [B6]-+/+, Fas-deficient B6-lpr/lpr, TNFRI-deficient B6-tnfr1(0/0), and B6-tnfr1(0/0)-lpr/lpr mice) were infected intraperitoneally with the Smith strain of MCMV (1 x 10(5) plaque-forming units). Viral load was determined by a plaque assay, inflammation and apoptosis by immunohistochemistry and staining with terminal dUTP nickend labeling, and autoantibodies by enzyme-linked immunosorbent assay.


RESULTS
Infectious MCMV was not detectable by day 100. Although all MCMV-infected mice developed acute sialadenitis by day 28, a chronic (>100 days), severe salivary gland inflammation and anti-Ro and anti-La antibodies developed only in the B6-lpr/lpr mice. Apoptotic cells were detected during the acute, but not the chronic, phase of inflammation.


CONCLUSIONS
Both Fas- and TNFRI-mediated apoptosis contribute to the clearance of MCMV-infected cells in the salivary glands. However, because Fas-mediated apoptosis is necessary for the down-modulation of the immune response, a defect in this process can lead to a postinfection, chronic inflammatory response that resembles Sjögren's syndrome.
Fleck
M
M
The University of Regensburg, Germany.
Kern
E R
ER
Zhou
T
T
Lang
B
B
Mountz
J D
JD
D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications*; D005260:Female; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018146:Muromegalovirus / Q000502:physiology*; D009154:Mutation; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology; D012469:Salivary Glands / Q000821:virology; D012793:Sialadenitis / Q000821:virology; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000821:virology; D019014:fas Receptor
D001323:Autoantibodies; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor