Human cytomegalovirus replication supported by virus-induced activation of CCL2–CCR2 interactions

• HCMV infection induced CCL2 expression at mRNA and protein levels.
• HCMV induced the mRNA expression of CCR2.
• CCL2 siRNA treatment reduced HCMV virion production.
• HCMV reduction by CCL2 siRNA was reversed by the addition of CCL2.

We previously revealed that human cytomegalovirus (HCMV) infection can cause aberrant expression of the chemokine IL-8/CXCL8. We first examined the effects of HCMV infection on the expression of another chemokine, CCL2. HCMV infection induced CCL2 expression at the mRNA and protein levels in human embryonic lung fibroblasts cells (HEL). Moreover, HCMV induced the mRNA expression of CCR2, a specific receptor for CCL2. CCL2 siRNA treatment reduced HCMV virion production, and this reduction was reversed by the addition of CCL2. We further observed that CCL2 siRNA, but not control siRNA, reduced the expression of HCMV immediate early gene (IE1) and HCMV UL54 gene (DNA polymerase) in a dose-dependent manner. Thus, HCMV infection is able to activate the CCL2–CCR2 interactions to further enhance HCMV infection and/or replication.