title: Cytomegalovirus infection aggravates atherogenesis in apoE knockout mice by both local and systemic immune activation.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. ivl@lmib.azm.nl
authors.forename: Inge
authors.initials: I
authors.lastname: Vliegen
authors.forename: Ad
authors.initials: A
authors.lastname: Duijvestijn
authors.forename: Gert
authors.initials: G
authors.lastname: Grauls
authors.forename: Selma
authors.initials: S
authors.lastname: Herngreen
authors.forename: Cathrien
authors.initials: C
authors.lastname: Bruggeman
authors.forename: Frank
authors.initials: F
authors.lastname: Stassen
mesh_terms: 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
chemical_list: D001057:Apolipoproteins E; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma