In situ detection of frequent and active infection of human cytomegalovirus in inflammatory abdominal aortic aneurysms: Possible pathogenic role in sustained chronic inflammatory reaction

Inflammatory abdominal aortic aneurysm (IAAA) is histopathologically characterized by extensive adventitial fibrosis, mononuclear cell infiltration with lymph follicle formation, and severe atheromatous changes in the aneurysmal wall. We previously reported a frequent prevalence and immediate early gene expression of human cytomegalovirus (CMV) in IAAA by solution-phase PCR and reverse transcription PCR, respectively, and suggested that this virus might play a role in chronic inflammatory reaction in IAAA. To evaluate the pathogenic role of CMV infection, the frequency and distribution of CMV infected cells in IAAA were examined by in situ PCR, and compared with those in atherosclerotic aneurysms (AA) and control cases with minimal atherosclerotic changes. Human leukocyte antigen (HLA)-DR was simultaneously evaluated as a marker for immune response related to CMV infection. Immediate early gene expression was also detected by reverse transcription PCR and in situ hybridization, to certify whether the CMV infection in IAAA is active or latent. In the fibrously thickened adventitia of IAAA, CMV infected cells and HLA-DR-positive cells were more frequently encountered than in that of AA and control cases (p < 0.01). CMV infected cells were largely identified as macrophages, fibroblasts, endothelial cells, and lymphocytes. The expression of CMV immediate early mRNA, which suggests an active infection inducing active inflammatory reaction, was detected in most of the macrophages, endothelial cells, and fibroblasts. Our results strongly suggest that frequent and active infection of CMV in IAAA plays a significant role in the induction and acceleration of chronic inflammatory reaction in aortas of IAAA.