Biology Reference
In-Depth Information
By analogy with the bacteriophage DNA packaging system, once pAP and pPR
are eliminated, DNA is incorporated with the help of the terminase-portal complex
(Fig. 4, step 7). Examples of intranuclear capsids apparently involved in this proc-
ess are shown in Fig. 6. The portal protein forms a 12-subunit homo-oligomeric
ring at a single vertex of the capsid through which the viral DNA can enter and
leave (Newcomb et al. 2001; Trus et al. 2004). At 29-Å resolution the HSV portal
complex resembles that of bacteriophage (Trus et al. 2004). Its CMV homolog,
pUL104, also appears restricted to a single capsid vertex (Dittmer and Bogner
2005). The herpesvirus DNA cleavage/packaging enzyme (terminase) is composed
of two subunits (Poon and Roizman 1993; Baines et al. 1994). The larger (HCMV
pUL56, 96 kDa) has properties consistent with it being a counterpart of the large
subunit of bacteriophage terminase (Bogner et al. 1993, 1995, 1998; Holzenburg
and Bogner 2002; Scheffczik et al. 2002): (a) it associates with a smaller subunit
(pUL89, 77 kDa, (b) it binds double-stranded viral DNA, and (c) it binds to the
capsid (White et al. 2003). Retention of DNA in the capsid is believed to be stabi-
lized by a protein (HCMV pUL7, 71 kDa) whose HSV homolog (pUL25, 60 kDa)
has a mutant phenotype that fails to stably package DNA (McNab et al. 1998;
Ogasawara et al. 2001; Sheaffer et al. 2001). This protein is considered a possible
counterpart of the bacteriophage cap protein, but may exert its effect by binding at
multiple sites on the capsid surface (Newcomb et al. 2006).
Tegumentation and Envelopment
The composition of the HCMV tegument and envelope, and the relationship of
their acquisition to virus egress from the nucleus and cell, have recently been
reviewed (Eickmann et al. 2006). The cartoon shown in Fig. 7 serves to summarize
some of the steps involved. A general consensus of data supports an envelopment/
de-envelopment mechanism for nuclear egress of herpesviruses, followed by final
envelopment through cytoplasmic membranes (Severi et al. 1988; Gibson 1993;
Enquist et al. 1998; Mettenleiter 2002; Leuzinger et al. 2005; Campadelli-Fiume
and Roizman 2006). As represented in Fig. 7, step 1, primary envelopment of the
capsid occurs at the inner nuclear membrane, enabling the particle to pass into the
perinuclear space.
Primary envelopment requires two herpesvirus group-conserved proteins. Their
HCMV homologs are pUL50 and pUL53; the respective HSV homologs are
pUL34 and pUL31 (Klupp et al. 2000; Roller et al. 2000; Reynolds et al. 2001;
Fuchs et al. 2002; Reynolds et al. 2002). HSV pUL34 localizes to both the inner
and outer leaflets of the nuclear membrane and is a substrate for the virion-associated
US3 protein kinase (Purves et al. 1992), which enhances its membrane localization
(Purves et al. 1992; Klupp et al. 2000, 2001; Roller et al. 2000; Reynolds et al.
2001, 2002). Although CMV does not encode a US3 homolog, the murine CMV
homolog of pUL34 (MCMV M50/p35) interacts with cellular protein kinase C and
carries it to the nuclear membrane where it is proposed to phosphorylate the
