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C
Inflammatory
stimuli
Maturation
stimuli
A
Mature DC
CD34+ cell
Myeloid differentiation
Reactivation
H
A
T
S
H
A
T
S
B
D
IE
NF-kB
NF-kB
IE genes
IE genes
MIEP
MIEP
AP1
AP1
Ac
Ac
Ac
Ac
Transcriptional Repression
HP-1
Transcriptional Activation
H
A
T
S
AP1
NF-kB
Fig. 3
Reactivation may be promoted by pro-inflammatory signals and is differentiation dependent. CD34
+
cells carry the HCMV genome in a latent form (
A
),
maintained by a repressive chromatin structure around the MIEP (
B
). Exposure of CD34
+
cells to growth factors and/or inflammatory cytokines promotes
myeloid differentiation to mature macrophages and dendritic cells (
C
). Differentiation is concomitant with changes in the levels of specific cellular transcrip-
tion factors and co-factors. These changes promote the reactivation of HCMV immediate-early gene expression, which is consistent with changes in the chro-
matin structure of the MIEP from a repressed to an active conformation (
D
). Whether this change is totally regulated by cellular factors or requires a viral
product remains unknown
