Biology Reference
In-Depth Information
modulators may exist in the virion (Varnum et al. 2004). Michelson et al. first
showed that HCMV virions contain serine/threonine protein phosphatase activity
due to the cellular protein phosphatases PP1 and PP2A (Michelson et al. 1996).
This work provided key evidence that HCMV captures cellular enzymes capable of
manipulating phosphorylation. Kinases are also present in the HCMV virion.
Gallina et al. showed that HCMV possess serine/threonine kinase activity due to
the cellular kinase, (polo-like kinase 1 (Plk1; Gallina et al. 1999)). Plk1 was shown
to interact with the major tegument protein, UL83/pp65, identifying a mechanism
in which cellular products could be captured by the virus during maturation through
a specific interaction with viral tegument proteins. We identified a second serine/
threonine kinase, casein kinase II (CKII), that is also incorporated into the mature
virion (Nogalski et al. 2007). The virion CKII possesses potent IκB kinase activity
and promotes the efficient transactivation of the major IE promoter (MIEP). Why
would the virus have evolved a mechanism to capture cellular enzymes? Reversible
phosphorylation via the reciprocal action of kinases and phosphatases is an effec-
tive and rapid mechanism for modulating cellular function (Arena et al. 2005); thus
this biochemical process is an attractive target for a virus that needs to rapidly
modulate the host cell for viral infection, survival and persistence. The release of
captured enzymes may allow an increase in the local concentration of those
enzymes in the viral microenvironment (Nogalski et al. 2007). It is also possible the
virion-associated enzymes have a different subcellular localization and thus poten-
tially different targets (Gallina et al. 1999). Additionally, because the virus infects
multiple cell types with different biological characteristics, the evolution of multi-
ple mechanisms to drive the rapid activation of the cell may ensure sufficient and
appropriate activation of each cell type following infection.
Tegument Protein-Mediated Signaling
HCMV possesses a number of tegument proteins that are able to modulate the host
cell, although many tegument proteins do not have identified functions (Mocarski
et al. 2007). Because another chapter will cover tegument proteins in detail (see the
chapter by R. Kalejta, this volume), the signaling potential of select tegument pro-
teins will only briefly be summarized. UL83, the major tegument protein, has been
shown to block the antiviral response through the inhibition of the cellular tran-
scription factors NFκ-B and interferon regulatory factor 1 (Browne and Shenk
2003). Other tegument proteins including UL82 (Schierling et al. 2004; Cantrell
and Bresnahan 2006a; Saffert and Kalejta 2006), UL35 (Schierling et al. 2004),
US24 (Feng et al. 2006) and UL26 (Stamminger et al. 2002; Munger et al. 2006)
can also influence the early events involved with MIEP transactivation and IE gene
expression. Tegument proteins also alter the cell cycle (reviewed in Kalejta and
Shenk 2002; Kalejta 2004; Mocarski et al. 2007). For example, UL82 promotes cell
cycle progression through the degradation of Rb family members (Kalejta et al.
2003; Kalejta and Shenk 2003a, 2003b), while UL69 blocks cell cycle progression
