Depletion of extracellular RANTES during human cytomegalovirus - Infectionof endothelial cells

Human cytomegalovirus (CMV) infection results in pneumonitis in bone-marrow and lung-transplant recipients. The source of CMV infection contributing t o the onset of pneumonitis is unclear, but may involve infection of the lun g endothelium in the presence of infiltrating mononuclear cells. Viral infe ction stimulates the host cell to express chemokines as signals to recruit specific immune cells to the site of injury. CMV encodes a chemokine recept or that may function to reduce host cell expression of chemokines. In the s tudy reported here we found that extracellular concentrations of the chemok ine regulated on activation, normal T cell expressed and secreted (RANTES) are depleted during productive infection of primary endothelial cells with CMV strain 4010, an endothelial-adapted strain of CMV. Utilizing adenovirus -transformed human kidney epithelial cells (type 293 cells) that stably exp ress the CMV-encoded chemokine receptor US28, we found that depletion of ex tracellular RANTES during infection is attributable to US28, which binds an d internalizes extracellular RANTES.