Chemistry Reference
In-Depth Information
17.2.5
Herpes viruses
A number of different herpes viruses capable of infecting humans exist. They
include
Herpes simplex
virus ( HSV ) - 1 and - 2, VZV, Epstein - Barr virus, HCMV,
and human herpesvirus-7 and -8 [18]. A shared feature for this group of viruses
is their binding to HS, which is found on almost all cells. The herpes viruses have
similar sets of envelope glycoproteins involved in cellular attachment and entry.
The tropism of the herpes viruses is not conserved to the same degree though.
HSV is an enveloped double-stranded DNA virus. It causes recurrent epidermal/
mucosal lesions, but can also cause encephalitis (HSV-1) and meningitis (HSV- 2).
At least 12 proteins are present in the envelope of HSV-1, of which glycoprotein B
( gB ), glycoprotein C ( gC ) and glycoprotein D (gD) interact with HS in different
steps of attachment and fusion. gC binding to HS requires an
N
- sulfated dodecamer
carrying at least one 2-
O -
and one 6-
O
- sulfate group [18]. Although similar, the
binding to HS is not identical between HSV-1 and -2 gC. The latter displays higher
avidity to HS, and the binding is more susceptible to heparin inhibition and HS
desulfation [18]. The HS-binding part of HSV-1 gC has been mapped to the
N
- ter-
minal region. gB is a type I membrane glycoprotein, which when mutated in the
poly-lysine HS-binding domain reduces the ability of HSV to bind to HS, although
to a lesser degree compared with mutated gC. gD is also a type I membrane glyco-
protein with three
N
-linked glycosylation sites. gD forms a dimer that requires 3-
O
-
sulfated groups to bind HS (please see Figures 1.7d and 11.1 for heparin structure).
HCMV is an opportunistic virus which can infect most human cell types. The
broad tropism indicates that the HCMV has several binding molecules in the
envelope and that the ligands are found on most cells. HS is required but not
suffi cient for infection. The complex proteins gM/gN and gB have been shown to
bind HS, where gB have several functions besides tethering [19]. gB is a spike
protein while gM is a type III glycoprotein with seven membrane-spanning
domains. gM is covalently bound to gN.
VZV causes a primary and a secondary disease - varicella (chickenpox) and
herpes zoster (shingles). Herpes zoster is caused by a reactivation of dormant
viruses residing in nerve ganglia after the primary infection. Infection is inhibited
by addition of mannose-6-phosphate. Moreover, cellular downregulation of MPR
also stops infection of VZV. This indicates that VZV binds to MPR via mannosyl-
ated envelope glycoproteins. gC is responsible for cellular attachment since viruses
with mutated gC are unable to bind to target cells. Reports suggest heparin, but
not chondroitin sulfate, protects cells from infection and that intact VZV particles
bind to heparin, underscoring specifi city.
17.2.6
Hepatitis C Virus
HCV is a small, enveloped, positive-stranded RNA virus of the Flaviviridae family
that infects the liver. The infection often becomes chronic, and may cause cirrhosis
