Chemistry Reference
In-Depth Information
strains have been shown to depend on GM1 and GM3 ganglioside binding for
infection. Sialidase-sensitive monkey rotavirus may utilize sialic acid on both gly-
colipids and glycoproteins.
The monomeric lectin, virus spike protein (VP) 4, mediates binding to sialic
acid and integrin
1
. VP4 is cleaved to form VP5* and VP8*, which interact with
integrins and sialic acids, respectively. VP8* has a
α
2
β
-sandwich fold similar to what
is found in galectins, even though there is no sequence similarity. The sialic acid
binding does not seem to be mediated by the galectin fold (for illustration, see
Figure 13.2); rather it is suggested to be localized to a shallow groove which is
conserved in sialic acid-dependent viruses [14]. Only VP8* from sialidase-sensitive
strains can be cocrystallized with Neu5Ac.
β
17.2.3
Human Immunodefi ciency Virus 1
Carbohydrate-mediated binding plays an important role in HIV-1 infection. The
envelope protein of HIV-1, gp120, and its binding to the lymphocyte accessory
molecule, CD4, and the chemokine receptor CCR5, have been well characterized.
The binding of gp120 to C-type lectins via high-mannose carbohydrates has also
been studied extensively. What is less described is the HIV gp120 binding to syn-
decans - type I transmembrane heparan sulfate (HS) proteoglycans (see Chapter
11.6 for further details of structure). For macrophages, it has been suggested that
the binding to long linear HS chains may mediate an initial attachment to the
target cell. This is followed by a scan for the entry receptors, that is, CD4 and
chemokine receptors [15] .
17.2.4
Norovirus
VP1 is the major capsid protein of Norovirus - a non - enveloped, positive - sense
single - stranded RNA virus. VP1 can self - aggregate to form virus - like particle s
(VLPs) consisting of 90 dimers of VP1. It has three domains, where the
N
- terminal
faces the interior, the shell domain constitutes the surface and the protruding
domain faces outwards. VLPs have been shown to bind to human blood group
antigens such as H type 1, A, B, Le
a
and Le
b
, preferably on mucins or mucin-like
proteins [16]. The binding of VP1 to different blood group antigens is strain spe-
cifi c, owing to the high genetic variability of VP1. Noroviruses are a major cause
of nonbacterial outbreaks of gastroenteritis. As individuals carry different blood
group antigens, natural resistance against some strains of Norovirus are prevalent
[17]. This is seen in the case of Norwalk virus strains that cause winter vomiting
disease, with approximately 20% of Caucasians being naturally resistant; they are
non-secretors lacking the H-type blood group antigens, and consequently A and
B antigens also, on epithelial cell surfaces. However, some Norovirus strains can
infect non-secretors as well [16].
