Fig. (2) Cellular transduction events occuring after macrophages infection by HCMV. (A) HCMV binds to the cellular EGFR through its glycoprotein gB and directly activates Akt, thus promoting an Akt-dependent prosurvival state. EGFR activation rapidly induces the expression of HSP27 and Mcl-1 that act together to downregulate caspase-3 activity and permit the virus persistence. (B) In the differentiated macrophages, NF-kB binding activity is increased allowing Bcl-3 to activate a number of human genes that favor cellular survival and optimal infection by HCMV. Activated p52/Bcl-3 complexes also act through the NF-kB sites to regulate the MIEP of HCMV and thus affecting the virus latency via HDACs. MIEP is also under by negative autoregulation through IE2 expression which in turn activates histone methyltransferases. EGFR: Epidermal Growth Factor Receptor ; HDACs: Histone Deacetylases ; HCMV: Human Cytomegalovirus ; MIEP: Major Immediate Early Promoter ; Bcl: B-cell lymphoma encoded protein ; gB: Glycoprotein B ; HSP: Heat Shock Protein ; IE: Immediate Early ; Mcl-1: Induced myeloid leukemia cell differentiation protein ; NF-kB: Nuclear Factor-Kappa B.

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