Enhanced atherogenesis is not an obligatory response to systemic herpesvirus infection in the apoE-deficient mouse: comparison of murine gamma-herpesvirus-68 and herpes simplex virus-1.
Viral and bacterial infectious agents have been implicated in the etiology of atherosclerosis. We have previously shown that a gamma-herpesvirus can accelerate atherosclerosis in the apolipoprotein E-deficient (apoE-/-) mouse. To address whether a virally induced systemic immune response is sufficient to trigger enhanced atheroma formation, we infected apoE-/- mice with murine gamma-herpesvirus-68 (MHV-68) or herpes simplex virus-1 (HSV-1). In this study, we show that both viruses were able to induce a cell-mediated and humoral immune response in the apoE-/- mouse, which was sustained over a period of 24 weeks. Although intranasal or intraperitoneal infection with MHV-68 induced similar levels of virus-specific IgG1 and IgG2a antibodies in the serum of apoE-/- mice, those infected with HSV-1 showed higher anti-HSV-1 IgG2a compared with IgG1 antibody levels. In addition, viral message was not detected in the aortas of HSV-1-infected animals, whereas we have shown previously that MHV-68 mRNA can be detected in the aortas of infected mice as early as 5 days after infection. Compared with control mice, apoE-/- mice infected with MHV-68 showed accelerated atherosclerosis, whereas mice infected with HSV-1 did not. These data indicate that a systemic immune response to any particular infectious agent is insufficient to induce enhanced atherosclerosis in the apoE-/- mouse and point to specific infections or immune mechanisms that might be essential for virally enhanced atherogenesis.
Alber
Dagmar G
DG
Wolfson Institute for Biomedical Research, University College London, London, UK. d.alber@ucl.ac.uk
Vallance
Patrick
P
Powell
Kenneth L
KL
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001011:Aorta / Q000821:virology; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000276:immunology / Q000821:virology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000302:isolation & purification; D018144:Rhadinovirus / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D013154:Spleen / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology; D014709:Vero Cells / Q000821:virology; D014776:Virus Cultivation / Q000379:methods
D000914:Antibodies, Viral; D001057:Apolipoproteins E; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D012367:RNA, Viral