Cytomegalovirus infection aggravates atherogenesis in apoE knockout mice by both local and systemic immune activation.
Since the 1970s, cytomegalovirus (CMV) infection has been associated with atherosclerotic disease. However, the exact contribution of the virus remains uncertain. In this article we describe both a direct and indirect immune-mediated effect of the virus on the disease process. Eight-week-old apolipoprotein E (apoE) knockout mice were infected with mouse CMV (MCMV) or mock injected, and they were sacrificed at 2 and 20 weeks post-injection (p.i.) to study atherosclerosis, vascular wall IFNgamma and TNFalpha expression and MCMV spread. To study plasma IFNgamma and TNFalpha levels, blood was collected at 1, 2, 4 and 6 days p.i. in addition to days of sacrifice. Plasma cytokine levels were increased after MCMV infection at early time points and decreased to mock levels at 2 and 20 weeks p.i. At 2 weeks p.i., more aortic arch samples showed local cytokine expression after MCMV infection. The number of early atherosclerotic lesions and the percentage of mice containing early lesions were increased at 2 weeks p.i., while at 20 weeks p.i., the MCMV-induced effect on atherogenesis was seen on the late lesions. In conclusion, MCMV infection induces a systemic immune response reflecting an indirect effect of MCMV infection on atherosclerosis in addition to a local aortic immune response reflecting a direct effect of the virus on the atherosclerotic process.
Vliegen
Inge
I
Department of Medical Microbiology, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. ivl@lmib.azm.nl
Duijvestijn
Ad
A
Grauls
Gert
G
Herngreen
Selma
S
Bruggeman
Cathrien
C
Stassen
Frank
F
D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004195:Disease Models, Animal; D007121:Immunocompetence; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000302:isolation & purification; D012469:Salivary Glands / Q000821:virology; D013154:Spleen / Q000821:virology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D001057:Apolipoproteins E; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma