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In-Depth Information
Fig. 1
HCMV binding to cognate receptors initiates signaling cascades. Binding of the envelope
glycoproteins, gB and gH, to the cellular receptors, EGFR, integrins and TLR2 begin the outside-
in signaling process observed in cells following infection. These known HCMV receptors are
integrated with cellular signal transduction pathways; thus viral ligand engagement is the stimulus
to fire downstream signaling processes. The initial receptor/ligand-directed signaling modulates a
number of pathways, of which a few examples are shown in the drawing. The consequences of
this outside-in signaling modulated by the viral glycoproteins include viral entry, cellular activa-
tion and transcriptional regulation of cellular and viral genes
adhesion kinase (FAK), the IKK cascade, the MAPK pathway, and the PI(3)K
pathway to promote both viral entry and cellular changes such as the activation of
NFκ-B and other transcription factors required for the transactivation of key cellu-
lar and/or viral genes (Fig. 1).
Captured Cellular Enzymes
The virion has long been known to harbor enzymatic activity (Mar et al. 1981),
although the nature of this signaling potential has been unresolved. The signaling
potential present in the virion imparts the virus with another mechanism to rapidly
mediate distinct cellular changes following infection. Two distinct signaling capa-
bilities are present in the virion: (1) HCMV captures cellular enzymes that directly
modify the host cell signaling capabilities following viral fusion (discussed in this
section) and (2) tegument proteins found in the mature virion can directly modulate
host cell biochemical pathways (discussed in the next section).
The virion contains at least four distinct functional enzyme activities of host cell
origin (Michelson et al. 1996; Gallina et al. 1999; Nogalski et al. 2007). A recent
mass spectrometry analysis of the HCMV proteome revealed that additional cellular
