Chemistry Reference
In-Depth Information
and liver cancer. Recent experiments have revealed that the binding and entry are
complex and engage several entry factors. The initial binding involves glycosami-
noglycans and lipoprotein lipase (LPL). HCV has two envelope glycoproteins, E1
and E2, which assemble to form a heterodimer and where both subunits are
responsible for interactions with HS. E1E2 are type I membrane proteins with a
C-terminal transmembrane domain and a larger
N
- terminal ectodomain. Direct
binding of E1 and E2 to heparin has been demonstrated in surface plasmon experi-
ments and HCV can be purifi ed using heparin columns. Heparin and heparinase,
an enzyme which degrades heparin, inhibit HCV binding.
N
- sulfation, but not
2 -
O
- and 6 -
O
-sulfation, is required for E1E2-HS interaction. When isolating HS
from liver and kidney, only liver HS can inhibit HCV binding [20]. Recently it was
shown that HCV associated with lipoproteins can use LPL to grant access to the
liver. LPL binds to HS at the cell surface of hepatocytes and act as a bridge to the
HCV-lipoprotein complex. Direct binding of HCV to HS on the cell surface may
still be of importance for infection yet.
17.2.7
Paramyxoviridae
Attachment to glycans on the cell surface is mediated by two types of glycoproteins
in paramyxoviruses, the attachment proteins Hemagglutinin/Neuraminidase
(HN) and glycoprotein G. HN is found on several paramyxoviruses including
Newcastle disease virus ( NDV ), human parainfl uenza virus (hPIV ) 1 - 4a and para-
infl uenza virus 5 (PIV 5). The HN lectin binds to, and removes, sialic acid in
various linkage positions when present in glycans of glycoproteins and ganglio-
sides. hPIV 1 recognizes
N
- acetyllactosamine with terminal
α
2,3 - linked Neu5Ac,
hPIV 3 prefers
N
- acetyllactosamine with terminal
α
2,3 - or
α
2,6 - linked Neu5Ac or
α
2,3-linked Neu5Gc [21]. Their HN lectin also bind to heparan sulfate. The HN
lectin of NDV has many targets, such as linear lacto-series oligosaccharides and
gangliosides, such as GM3, GD1a, GT1b, GM2, GM1 or GD1b [21] .
The G glycoprotein is expressed by respiratory syncytial virus (RSV) and henipa-
viruses (Nipah and Hendra). RSV-G binds to HS where a minimal requirement
for binding is a decasaccharide with
N
- sulfated residues [18]. It lacks hemaggluti-
nation and NA activity. RSV-G is found as an anchored type II membrane protein
and as a smaller, soluble form without the
N
- terminal [21]. The protein is highly
glycosylated in mucin-like regions, with glycans contributing to 60% of the weight.
Sequence and structural homology comparison reveal similarity to a subdomain
of tumor necrosis factor receptor.
In the sections above we have learned that cell-surface carbohydrates play an
important role also in viral infections. As for bacteria, lectin binding is specifi c, but
the individual receptor-ligand interaction is often of low affi nity. However, because
viruses, just as bacteria, adhere to host cells via multiple binding points, the overall
binding avidity is very high and viral adhesion therefore in principle irreversible.
For many bacterial and viral species, lectin binding to cell-surface carbohydrates
is essential for infection to occur. Once the structure-function relationships in the
