Ccl5-Dependent Replication Of Human Cytomegalovirus Is Inhibited By Tricin In Vitro

Background: Human cytomegalovirus (HCMV) infection is a widespread opportunistic pathogen in immunocompromised individuals. So, HCMV infection is still associated with severe morbidity and mortality. HCMV can enhance the expression of a CC chemokines. HCMV infection is presumed to contribute to atherosclerosis, where chemokines may have a pathogenic role. Elevated levels of RANTES (CCL5) are observed in atherosclerotic plaques. HCMV and CCL5 may cooperatively contribute to atherosclerosis. Our recent study revealed that tricin (4′,5,7-trihydroxy-3′,5′- dimethoxyflavone) has anti-HCMV activity in a human embryonic lung fibroblast cells (HEL). In the present study, we revealed that HCMV-induced CCL5 expression further augments HCMV infection and that tricin exerts its anti-HCMV activity by targeting CCL5. Methods & Materials: HEL cells were treated with tricin after HCMV infection. Total RNA was then extracted at 24 h after infection and subjected to detect CCL5 mRNA or proteins were then extracted to detect CCL5 protein. HEL cells were infected with HCMV at 24 h after CCL5 siRNA transfection. At 6 days after infection, supernatants were collected to determine virus titer. Results: Tricin inhibited HCMV replication, with concomitant decreases in the levels of transcripts of the CCL5 gene and in the accumulation of the CCL5 protein. We also found that the replication of HCMV was significantly lower in CCL5 gene-knockdown cells. Conclusion: These results suggested that CCL5 represents an attractive anti-cytomegalovirus target, and that tricin may be a good candidate for novel anti-HCMV agent.