Biology Reference
In-Depth Information
Activities for less than half of the tegument proteins have been determined
or suggested (Table 1). The phenotypes of recombinant viruses with null mutations
in genes encoding tegument proteins demonstrate that some are absolutely essential
for viral replication, others are required for efficient replication (often termed aug-
menting genes), while still others are dispensable for lytic replication in vitro
(Mocarski et al. 2007; Dunn et al. 2003; Yu et al. 2003). Many tegument proteins
play important roles during the later stages of viral replication, and are required for
proper viral assembly and egress (see the chapter by W. Gibson, this volume). This
review focuses on the functions of tegument proteins during the initial intracellular
events of a lytic infection, after fusion of the viral and cellular envelopes, but prior
to the transcription of the first viral genes to be expressed from the infecting viral
genome, the immediate early (IE) genes. Thus, what are described here are called
postfusion, preimmediate early events.
Tegument Proteins Known to Act at the Very Start
of HCMV Infection
The pp65 phospho-protein is the major constituent of HCMV particles (Irmiere and
Gibson 1983) and is delivered to the nucleus of permissive cells after fusion of the viral
and cellular membranes (Revello et al. 1992). pp65 is either itself a protein kinase (Yao
et al. 2001) or associates with a cellular kinase (Gallina et al. 1999) or perhaps both.
If pp65 does have intrinsic kinase activity, it is an unusual example of a kinase because
it shows poor homology to the catalytic domain sequences of other kinases (Yao et al.
2001). The UL83 gene that encodes pp65 is completely dispensable for replication in
cultured fibroblasts (Schmolke et al. 1995), but is likely maintained despite the pres-
ence of strong, targeted immune response (Grefte et al. 1992; Wills et al. 1996)
because of the ability of pp65 to modulate multiple levels of immune surveillance
(Mocarski et al. 2007). Monitoring the delivery of tegument-incorporated pp65 to the
nucleus is a common method used to assay for viral entry. Recently, pp150, the second
most abundant tegument protein, has also been used to track viral entry (see Sect. 3
below). Encoded by UL32, a gene absolutely essential for lytic replication in vitro
(Dunn et al. 2003; Yu et al 2003), pp150 interacts with preformed capsids (Baxter and
Gibson 2001), and appears to be required for the incorporation of capsids into forming
virions, perhaps because of its ability to stabilize capsids and/or direct their movement
within the cytoplasm (Aucoin et al. 2006).
The UL47 and UL48 tegument proteins form a complex with each other and the
major capsid protein (Bechtel and Shenk 2002) that appears to play a prominent
role during viral entry (see Sect. 3 below). pUL47 has no known enzymatic activity,
but pUL48 is a deubiquitinating protease (Wang et al. 2006). While the deubiquiti-
nating activity is not absolutely essential for viral replication, clones with active site
mutations in pUL48 show temporal delays in virion release (Wang et al. 2006).
Thus, along with their roles in viral entry, pUL47 and pUL48 also likely function
during viral maturation and/or egress. UL47 is an augmenting gene, disruption of
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