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(Schierling et al. 2005). Other assembly/egress defects were also noted. Thus, pUL35
may control the incorporation of other viral proteins (such as pp71) into the tegument.
Lower levels of pp71 in UL35-null virions could explain the delay in IE gene expres-
sion observed after infection with the mutant virus. A quantitative comparison of
tegument proteins incorporated into wild type and UL35-null virions is thus an essen-
tial experiment. As pUL35 is only a minor component of the tegument (Varnum
et al. 2004), it may have a catalytic (as opposed to stoichiometric) role in tegument
assembly, perhaps by influencing nucleocytoplasmic transport pathways, as has been
hypothesized (Schierling et al. 2005).
pUL26 is also a minor component of virions (Varnum et al. 2004) that is required
for efficient viral replication (Dunn et al. 2003; Yu et al. 2003; Lorz et al. 2006;
Munger et al. 2006) and may have an indirect role in the activation of IE gene
expression by pp71. In the absence of pUL26, the phosphorylation and stability of
at least one tegument protein (Munger et al. 2006) and the stability of virions them-
selves (Lorz et al. 2006) is reduced. Thus pUL26 appears to play a role in tegument
assembly/disassembly, and/or tegument protein/virion stability. How pUL26 may
modulate the functions of tegument proteins that act at postfusion, preimmediate
early times such as pUL47, pUL48, and pp71 remains to be determined.
In addition to Daxx, the PML protein itself also inhibits HCMV IE gene expres-
sion (Tavalai et al. 2006). However, the newly synthesized IE1 protein disrupts
PML-NBs (Korioth et al. 1996) and neutralizes the repressive effects of PML and
perhaps other PML-NB proteins (Tavalai et al. 2006). Interesting points for further
study include determining if PML can be recruited to infecting HCMV genomes
in the absence of Daxx, and if Sp100 or any other PML-NB protein also represses
HCMV gene expression. We know that at least two PML-NB proteins (Daxx and
PML) can repress HCMV IE gene expression, that these structures are sequentially
dismantled during HCMV infection, and that HCMV replicates to higher titers in
the absence of at least two PML-NB proteins (Daxx and PML), which strongly
argues that PML-NBs are not preferred sites of viral transcription and replication,
but that the proteins that localize to these structures have antiviral functions.
Because these proteins are constitutively expressed, they have been characterized
as mediators of intrinsic immunity against HCMV (Saffert and Kalejta 2006;
Tavalai et al. 2006), analogous in their effects to retroviral restriction factors
(Bieniasz 2004).
Model for Postfusion, Preimmediate Early Events
This section describes an overly simplified model for postfusion, preimmediate
early events during HCMV lytic infection of fully permissive fibroblasts (Fig. 1).
The model is based on experiments with HCMV, data from other herpesviruses, and
a certain amount of speculation on the part of the author. It is not meant as a com-
prehensive, definitive picture, but as a working model that needs to be refined and
built upon.
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