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Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Human cytomegalovirus infection in human renal arteries in vitro
Barbara Reinhardt1, Bianca Vaida, Rainer Voisard
1Abteilung Virologie, Institut fur Mikrobiologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Insights
Human cytomegalovirus (HCMV) may contribute to atherosclerosis. A novel human renal artery organ culture model demonstrates long-lasting HCMV infection, revealing strain-specific differences in arterial cell tropism and viral spread.
Area of Science:
- Vascular Biology
- Virology
- Immunology
Background:
- Human cytomegalovirus (HCMV) is implicated in atherosclerosis development.
- Existing cell culture models and animal models are insufficient for studying HCMV's role in atherosclerosis pathogenesis.
Purpose of the Study:
- To establish and validate a human renal artery organ culture model for in vitro HCMV infection.
- To investigate HCMV strain-specific tropism and infection kinetics within human arteries.
Main Methods:
- Development of an organ culture system using human renal arteries.
- Infection of artery segments with three distinct HCMV strains.
- Detection of infectious virus, viral DNA (in situ PCR), and viral antigens (immunohistochemistry).
Main Results:
- Long-lasting productive HCMV infection was observed in the organ culture model (up to 144 days).
- HCMV strains exhibited differential cell tropism and kinetics, affecting endothelial cells and lamina media.
- HCMV DNA was detected in both infected and some non-infected arteries from seropositive donors, but early antigen was only in infected segments.
Conclusions:
- The established organ culture model provides a more physiological environment for studying HCMV infection in human arteries.
- This model allows for detailed investigation of HCMV strain variations and their impact on vascular tissue.
- Further research using this model can elucidate the functional and molecular consequences of HCMV in atherosclerosis.
Abstract:
Studies with animal cytomegaloviruses, epidemiological data from humans as well as in vitro studies suggest the involvement of the human cytomegalovirus (HCMV) in the development of atherosclerosis. Cell culture systems are insufficient for examination of the entire pathogenetic process and a satisfactory animal model for HCMV is not available. An organ culture model was established for HCMV infection of human renal arteries in vitro. After infection with three representative HCMV strains, infectious virus was recovered from supernatants until 144 days post-infection with a peak around day 30 due to a long-lasting productive HCMV infection in still vital cells. Differences in cell tropism and kinetics of infection were identified between the HCMV strains. Specifically, differences in infecting endothelial cells and virus penetration into the lamina media were observed. In infected artery segments, but also in some non-infected arteries from seropositive donors, HCMV DNA could be localized by in situ PCR. Nevertheless, HCMV early antigen was detected by immunohistochemistry exclusively in artery segments infected in vitro. The new organ culture model will permit the study of functional and molecular consequences of HCMV infection in a more physiological micro-environment.
