Cytomegalovirus-caused release of collagenase IV from human cerebral microvascular endothelial cells.
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.


METHODS
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.
Poland
S D
SD
Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Dekaban
G A
GA
Costello
P C
PC
Rice
G P
GP