Abstract
Human cytomegalovirus (HCMV) is the major infectious cause in immunocompromized individuals. The expression of several cellular proteins involved in modulating cellular DNA replication is increased during HCMV infection. Proliferating cell nuclear antigen (PCNA) is a key protein participating in cellular DNA replication. To determine whether PCNA expression is induced by HCMV, we had investigated the protein, mRNA level, and promoter activity of PCNA and its localization in the nucleus during HCMV infection. We found that HCMV stimulates the synthesis of both protein and mRNA of PCNA and the activation of PCNA promoter indicating that PCNA might be induced by HCMV at the transcriptional level. This hypothesis was further supported by the finding that HCMV viral immediate early protein 1 (IE1) significantly activated PCNA promoter activity. Moreover, PCNA exhibited granular structure in the nucleus and was colocalized with viral polymerase accessory factor UL44 and immediate early protein 2 (IE2) when fibroblasts were infected with HCMV. These results indicate that PCNA is specifically activated by HCMV viral protein IE1 and is possibly recruited to the viral replication center. These results suggest that PCNA may be involved in HCMV DNA replication.