Protein Kinases in Human Cytomegalovirus Infection and Gene Expression

Infection of human fibroblast cells with human cytomegalovirus (HCMV) resulted in an increase in protein kinase A (PKA) activity measured at 6 h after virus infection. Protein kinase C (PKC) activity increased gradually until 12 h of HCMV infection. The pattern of the increase in PKA or PKC activity demonstrated a close relationship with the increase in the intracellular level of cAMP or Ca2+, respectively. The increase in PKA activity may be related to the stimulation of HCMV major immediate early (MIE) gene expression since the treatment of HCMV-infected cells with stimulators of PKA, including forskolin or bromo-cAMP enhanced the transcription of the MIE gene measured 6 h after HCMV infection. A similar result was obtained when HCMV-infected cells were treated with activators of PKC such as TPA and DOG. On the other hand, verapamil and nifedipine, well-known blockers of Ca2+ influx, suppressed the transcription of the MIE gene. Thus our results demonstrate that there is a strong correlation among the intracellular levels of cAMP and Ca2+, protein kinase activities, and MIE gene expression in HCMV infection of permissive human fibroblast cells.