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Published on: July 24, 2016
Cytomegalovirus-caused release of collagenase IV from human cerebral microvascular endothelial cells
S D Poland1, G A Dekaban, P C Costello
1Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Background:
Human cytomegalovirus (HCMV) in most normal individuals results in an asymptomatic infection, but under some circumstances, such as in the transplant setting, AIDS and intrauterine infection of the fetus, HCMV infection can lead to more serious consequences, including central nervous system infection. Recently it has been demonstrated that HCMV-infected endothelial cells can be detected in the circulation; however, no mechanism has been suggested.
Objective:
To determine whether HCMV infection of confluent human microvascular endothelial cells (HMEC) in culture results in the induction of type IV collagenase. This would provide a mechanism by which HCMV-infected HMECs could be released into the circulation.
Study Design:
Confluent cultures of brain-derived HMECs were infected with HCMV and culture supernatants were sampled for collagenase IV, general protease and viral titers.
Results:
HCMV infection of HMECs stimulated a significant release of collagenase type IV activity which peaked early in the assay within 3-5 days and fell off rapidly thereafter. This stimulation of protease activity differed only slightly between non-infected and infected cultures. By day 6, viral cytopathic effects became evident and HCMV titers reached approximately 5 x 10(5) PFU/ml by day 9.
Conclusions:
These results demonstrate that HCMV infection of HMEC induces the release of collagenase type IV. This may lead to the degradation of the basement membrane and subsequently to the release of fully infected endothelial cells into the circulation resulting in further dissemination of the infection.
Insights
Human cytomegalovirus (HCMV) infection of endothelial cells triggers collagenase type IV release. This mechanism may explain how infected cells enter circulation, potentially spreading HCMV infection.
Area of Science:
- Virology
- Cell Biology
- Pathogenesis
Background:
- Human cytomegalovirus (HCMV) typically causes asymptomatic infections but can lead to severe complications, including CNS infections, in immunocompromised individuals and fetuses.
- HCMV-infected endothelial cells have been detected in circulation, but the underlying mechanism remains unclear.
Purpose of the Study:
- To investigate if HCMV infection induces type IV collagenase in human microvascular endothelial cells (HMECs).
- To elucidate a potential mechanism for HCMV-infected HMEC release into the bloodstream.
Main Methods:
- Confluent brain-derived HMEC cultures were infected with HCMV.
- Culture supernatants were analyzed for collagenase IV, general protease activity, and viral titers.
Main Results:
- HCMV infection significantly increased collagenase type IV activity in HMECs, peaking at 3-5 days post-infection.
- Viral cytopathic effects and HCMV titers (approx. 5 x 10(5) PFU/ml) became evident by day 6-9.
Conclusions:
- HCMV infection of HMECs induces collagenase type IV release.
- This protease activity may degrade the basement membrane, facilitating the release of infected endothelial cells into circulation and promoting viral dissemination.
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