Related Experiment Video
Updated: Jul 13, 2026
An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
Published on: August 25, 2017
HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia
Rainer Voisard1, Tanja Krügers, Barbara Reinhardt
1Department of Internal Medicine II-Cardiology, University of Ulm, Ulm, Germany. rainer.voisard@uni-ulm.de
Insights
Human cytomegalovirus (HCMV) infection does not appear to trigger restenosis by stimulating cell proliferation. However, the study observed strain-specific differences in neointimal hyperplasia following HCMV infection.
Area of Science:
- Vascular Biology
- Virology
- Immunology
Background:
- The role of human cytomegalovirus (HCMV) in atherosclerosis and restenosis remains unclear, with conflicting findings from clinical studies.
- Previous research has yielded contradictory results regarding the correlation between HCMV infection and cardiovascular diseases.
Purpose of the Study:
- To investigate the effect of in vitro HCMV infection on cell proliferation and neointimal hyperplasia.
- To utilize a human ex vivo organ culture model to assess HCMV's impact on vascular changes over 56 days.
Main Methods:
- Human renal artery segments were cultured ex vivo and infected with different HCMV strains (AD169, TB40E, AN 365) or mock-infected.
- Cell proliferation and neointimal thickening were analyzed at multiple time points up to 56 days post-infection.
Main Results:
- Successful HCMV infection was confirmed for all tested strains.
- No significant cell proliferation or neointimal hyperplasia was observed in the first 21 days.
- Moderate neointimal hyperplasia occurred at 35 and 56 days in both infected and control groups, with lower hyperplasia in HCMV-infected segments compared to controls, except for the TB40E strain.
Conclusions:
- The findings do not support the hypothesis that HCMV infection stimulates cell proliferation and neointimal hyperplasia, thereby triggering restenosis.
- A notable virus strain-specific difference in neointimal hyperplasia was observed even after lytic HCMV infection.
Background:
The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.
Results:
During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains.
Conclusion:
The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.
