Effects of murine norovirus on atherosclerosis in ldlr(-/-) mice depends on the timing of infection.
We previously reported that murine norovirus (MNV), a virus prevalent in United States research institutions, increased atherosclerotic lesion size in Ldlr(-/-) mice when the mice were infected 8 wk after feeding an atherogenic diet. To determine whether the timing of MNV infection relative to atherosclerosis development altered the disease phenotype and to examine potential mechanisms by which MNV influences the disease process, we fed Ldlr(-/-) mice an atherogenic diet for 16 wk. Three days after initiating the atherogenic diet, half of the mice received MNV4 and the other half vehicle only (clarified cell-culture lysate; controls). Both groups of mice developed large aortic sinus lesions (control compared with MNV4: 133 ± 8 × 10³ μm² compared with 140 ± 7 × 10³ μm²) that were not significantly different in size. Because the timing of MNV infection relative to atherosclerosis development and hypercholesterolemia differed between our previous and the current studies, we examined whether hypercholesterolemia altered MNV4-induced changes in bone-marrow-derived macrophages. MNV4 infection increased the potential of macrophages to take up and store cholesterol by increasing CD36 expression while suppressing the ABCA1 transporter. Thus, the effects of MNV4 infection on atherosclerotic lesion size appear to be dependent on the timing of the infection: MNV4 infection promotes only established lesions. This effect may be due to MNV4's ability to increase cholesterol uptake and decrease efflux by regulating CD36 and ABCA1 protein expression.
The Department of Comparative Medicine, University of Washington, Seattle, Washington, USA. jpaik@uw.edu.
Jisun
J
Paik
The Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Fiona
F
Kwok
The Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Audrey
A
Seamons
The Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Thea
T
Brabb
The Department of Medicine, University of Washington, Seattle, Washington, USA.
Jinkyu
J
Kim
The Department of Medicine, University of Washington, Seattle, Washington, USA.
Brittany
B
Sullivan
The Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Charlie
C
Hsu
The Department of Medicine, University of Washington, Seattle, Washington, USA.
Kevin D
KD
O'Brien
The Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
Lillian
L
Maggio-Price
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000821:virology*; D018955:CD36 Antigens / Q000378:metabolism; D017250:Caliciviridae Infections / Q000150:complications*; D002784:Cholesterol / Q000378:metabolism; D004036:Diet, Atherogenic / Q000009:adverse effects; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000150:complications; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D029322:Norovirus / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors
D064286:ATP Binding Cassette Transporter 1; D018955:CD36 Antigens; D002784:Cholesterol; D012333:RNA, Messenger; D011973:Receptors, LDL; C577833:Abca1 protein, mouse