Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms.MicroRNAs (miRNAs),which function as post-transcriptional regulators,are utilized by human cytomegalovirus (HCMV) in its infection and pathogenesis.In the present study,the DNA replication inhibitor Geminin (GMNN) was identified to be a direct target of hcmv-miR-US5-1.Overexpression of hcmv-miR-US5-1 could block the accumulation of GMNN during HCMV infection,and the decrease of GMNN expression caused by hcmv-miR-US5-1 or GMNN specific siRNA reduced HCMV DNA copies in U373 cells.Meanwhile,ectopic expression of hcmv-miR-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation.These results imply that hcmv-miR-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.