Human cytomegalovirus protects endothelial cells from apoptosis induced by growth factor withdrawal.
The placental and umbilical blood vessel endothelia may play an important role in human cytomegalovirus (CMV) transmission and viral propagation in the fetus. We propose that CMV infection promotes endothelial cell viability for virus replication. Furthermore, we suggest that certain viral mechanisms are established to delay or inhibit the cellular response to undergo apoptosis. We have established a model of CMV infection in primary endothelial cells (HUVECs) in which productive infection with the endothelial-adapted strain of CMV, strain 4010, inhibits apoptosis induced by growth factor withdrawal. Apoptosis was measured by assessment of nuclear changes by TUNEL staining. Our results indicate that CMV infection at 48-96 h significantly protects the endothelial cell from apoptosis induced by growth factor withdrawal. We found that uninfected cells in the CMV-infected cell cultures, but not CMV-infected cells, were susceptible to apoptosis during growth factor withdrawal. Our studies examine the pro-apoptotic pathways that are inhibited and the anti-apoptotic pathways that are activated during CMV infection. The pro-apoptotic protein, caspase-3, is activated during growth factor withdrawal in mock-infected HUVECs, but activation is reduced in CMV-infected HUVECs. During infection, the CMV-encoded chemokine receptor US28 is expressed on the infected cell surface. Previously, we have shown that stimulation of US28 with the chemokine RANTES activates cellular proliferative responses in endothelial cells. It is likely, therefore, that US28 might activate anti-apoptotic mechanisms during CMV infection.
PubMed Abstracts
PubMed Abstracts