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receptors and/or ubiquitously expressed receptors, a fact that has challenged
researchers in the search for cellular receptors.
It is known that HCMV entry begins with an initial tethering step to heparan
sulfate proteoglycans (HSPGs) on the cell surface, mediated by gB and gM (Kari
and Gehrz 1992, 1993; Compton et al. 1993). At least in vitro, binding to HSPGs
is an essential step in the HCMV entry process and is thought to help stabilize the
virion at the cell surface until other downstream receptors are engaged (Compton
et al. 1993). This is supported by the biphasic binding properties of a soluble
form of gB, which in HSPG-null cells reverts to single-kinetic binding (Boyle and
Compton 1998). Additionally, HCMV virions are initially dissociable from the
cell surface by soluble heparin; however, the virus quickly moves to a heparin-
resistant binding state (Compton et al. 1993). These data suggest that an additional
receptor(s) is being engaged by HCMV, most likely via gB, following attachment
to HSPGs.
Over the past 25 years, several HCMV receptors have been initially identified,
only upon more stringent testing, to discover that they did not fulfill the require-
ments of an entry receptor (Table 1). It was discovered that HCMV associated
with β 2 -microglobulin (β 2 m), which led to the hypothesis that β 2 m-coated HCMV
particles bound the α chain of the HLA class I antigens, displacing endogenous
β 2 m (McKeating et al. 1986; Grundy et al. 1987a, 1987b; McKeating et al. 1987).
However, β 2 m did not bind envelope proteins as expected, but instead associated
with the tegument (Stannard 1989). Additionally, preincubating cells with anti-
bodies to MHC class I molecules did not inhibit HCMV infectivity and cell lines
differentially expressing MHC class I molecules or β 2 m showed no correlation
with HCMV infection (Beersma et al. 1990, 1991, 1992; Wu et al. 1994).
A 30-kDa HCMV receptor was identified by binding radiolabeled HCMV
particles to cell lysate blots (Adlish et al. 1990; Taylor and Cooper 1990). Virus
attachment correlated with the abundance of the receptor but penetration did not,
suggesting the receptor acted at the attachment stage only (Nowlin et al. 1991).
The receptor was eventually identified as annexin II, which is known to interact
with phospholipid membranes and has been implicated in the bridging and fusion
of membranes (Wright et al. 1994). HCMV virions were found to bind annexin II,
via gB, an event which increased virus binding and fusion (Pietropaolo and
Table 1 Proposed HCMV cellular receptors
Interacting HCMV
Currently considered
Cellular receptor
glycoprotein
HCMV entry receptor?
HSPG
gB and gM
Yes
MHC class I molecules
None identified
Unlikely
Annexin II
gB
Accessory role?
CD13
None identified
Unlikely
92.5 KDas receptor
gH
More data needed
EGFR
gB
More data needed
α
2
β
1,
α
6b1,
α
V
β
3 integrins
gB and gH
Yes
 
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