Effects of Murine Norovirus on Chlamydia pneumoniae-Accelerated Atherosclerosis in ApoE(-/-) Mice.
Chlamydia pneumoniae (Cpn), a common respiratory pathogen of humans, is associated with human cardiovascular disease and the acceleration of atherosclerosis in hyperlipidemic animal models. Our laboratory has demonstrated that murine norovirus (MNV), a prevalent infection of laboratory mice, can unpredictably alter atherosclerosis in hyperlipidemic Ldlr(-/-) and ApoE(-/-) mice. Given that MNV has a tropism for macrophages and may exacerbate atherogenesis, we investigated whether coinfection with MNV and Cpn might alter macrophage phenotypes in vitro and atherosclerosis in ApoE(-/-) mice. In the presence of oxidized low-density lipoprotein, coinfection of ApoE(-/-) bone marrow-derived macrophages (BMDM) with MNV and Cpn resulted in significant increases in gene expression of IL6, MCP1, iNOS, and TNFα compared with Cpn-monoinfected BMDM. On the basis of these findings, we hypothesized that concurrent MNV-Cpn infection might increase plaque lesion size in vivo. As expected, Cpn monoinfection of ApoE(-/-) mice increased mean plaque size by 62% compared with that in uninfected mice. However, MNV did not significantly alter plaque lesion size in MNV-Cpn-coinfected mice compared with Cpn-monoinfected mice. There were no differences in aortic cytokines locally at the site of plaque development or in peritoneal macrophages at 1 wk after infection in MNV-Cpn-coinfected mice compared with Cpn-monoinfected mice. MNV was not detected in the aortic tissue of MNV-infected mice at 1 or 8 wk after infection regardless of Cpn status. These data suggest that MNV infection does not appreciably alter plaque development in Cpn-accelerated atherosclerosis in ApoE(-/-) mice.
Departments of Comparative Medicine, University of Washington, Seattle, Washington, USA kpatil@uw.edu.
Karuna
K
Patil
Departments of Epidemiology, University of Washington, Seattle, Washington, USA.
Lee Ann
LA
Campbell
Departments of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA.
Michael E
ME
Rosenfeld
Departments of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Jisun
J
Paik
Departments of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Thea
T
Brabb
Departments of Medicine, University of Washington, Seattle, Washington, USA.
Kevin D
KD
O'brien
Departments of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Lillian
L
Maggio-Price
Departments of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Charlie C
CC
Hsu
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications* / Q000473:pathology; D017250:Caliciviridae Infections / Q000150:complications*; D018932:Chemokine CCL2 / Q000378:metabolism; D016993:Chlamydophila pneumoniae; D060085:Coinfection / Q000150:complications; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D029322:Norovirus / Q000302:isolation & purification; D018410:Pneumonia, Bacterial / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001057:Apolipoproteins E; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse