title: Murine norovirus increases atherosclerotic lesion size and macrophages in Ldlr(-/-) mice.
abstract: Murine norovirus (MNV) is prevalent in rodent facilities in the United States. Because MNV has a tropism for macrophages and dendritic cells, we hypothesized that it may alter phenotypes of murine models of inflammatory diseases, such as obesity and atherosclerosis. We examined whether  MNV infection influences phenotypes associated with diet-induced obesity and atherosclerosis by using Ldlr(-/-) mice. Male Ldlr(-/-) mice were maintained on either a diabetogenic or high-fat diet for 16 wk, inoculated with either MNV  or vehicle, and monitored for changes in body weight, blood glucose, glucose tolerance, and insulin sensitivity. Influence of MNV on atherosclerosis was analyzed by determining aortic sinus lesion area. Under both dietary regimens, MNV-infected and control mice gained similar amounts of weight  and developed similar degrees of insulin resistance. However, MNV infection was associated with significant increases in aortic sinus lesion area and macrophage content in Ldlr(-/-) mice fed a high-fat diet but not those fed a diabetogenic diet. In conclusion, MNV  infection exacerbates atherosclerosis in Ldlr(-/-) mice fed a high-fat diet but does not influence obesity- and diabetes-related phenotypes. Increased lesion size was associated with increased macrophages, suggesting that MNV may influence macrophage activation  or accumulation in the lesion area.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Jisun
authors.initials: J
authors.lastname: Paik
authors.forename: Yvette
authors.initials: Y
authors.lastname: Fierce
authors.forename: Phuong-Oanh
authors.initials: PO
authors.lastname: Mai
authors.forename: Susan R
authors.initials: SR
authors.lastname: Phelps
authors.forename: Thomas
authors.initials: T
authors.lastname: McDonald
authors.forename: Piper
authors.initials: P
authors.lastname: Treuting
authors.forename: Rolf
authors.initials: R
authors.lastname: Drivdahl
authors.forename: Thea
authors.initials: T
authors.lastname: Brabb
authors.forename: Renee
authors.initials: R
authors.lastname: LeBoeuf
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: Lillian
authors.initials: L
authors.lastname: Maggio-Price
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000830:Animals, Laboratory; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology*; D001786:Blood Glucose; D001835:Body Weight; D017250:Caliciviridae Infections / Q000150:complications / Q000662:veterinary*; D059305:Diet, High-Fat / Q000662:veterinary; D006652:Histological Techniques / Q000662:veterinary; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D029322:Norovirus; D011973:Receptors, LDL / Q000235:genetics*; D012376:Rodent Diseases / Q000821:virology*; D014481:United States
chemical_list: D001786:Blood Glucose; D011973:Receptors, LDL