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present endogenously synthesized antigenic peptide fragments to
cytotoxic T lymphocytes. SV40 binding to cells can be blocked by two
monoclonal antibodies against class I human lymphocyte antigen
(HLA) proteins but not by monoclonal antibodies specific for other
cell surface proteins. Also, SV40 does not bind to cells of two differ-
ent human lymphoblastoid cell lines which do not express surface
class I MHC proteins because of genetic defects in the
2-microglob-
ulin gene in one line and in the HLA complex in the other. Transfection
of these cell lines with cloned genes for
β
2-microglobulin and HLA-
B8, respectively, restored expression of their surface class I MHC pro-
teins and resulted in concomitant SV40 binding. Finally, SV40 binds
to purified HLA proteins
in vitro
and selectively binds to class I MHC
proteins in a surface extract. These proteins are an essential compo-
nent of the cell surface receptor for SV40. For the polyomavirus
receptor molecules, it has been shown that infectivity of the poly-
omavirus A2 strain in mouse Swiss 3T3 fibroblasts, is significantly
reduced only in the presence of natural integrin ligands carrying an
LDV motif or antibodies directed against the alpha4 and beta1 inte-
grin subunit in the alpha4-deficient BALB/c 3T3 cells, increases viral
infectivity.
34
Addition of alpha4 function-blocking antibodies, prior to
or after virus adsorption, blocks this increased infectivity without
affecting virus binding to cells. These data indicate that expression of
alpha4 integrin enhances permissivity to polyomavirus, probably by
acting as one of the post-attachment receptors.
The important role of sialic acid in the adsorption of polyoma-
virus to cells was first demonstrated by the abolition of viral-
mediated hemagglutination upon treatment of erythorocytes with
neuraminidase.
35-37
Neuraminidase has also been used successfully to
prevent polyomavirus infection of cultured mouse embryo cells. These
observations provide evidence for sialic acid as an integral component
of the cell surface receptors for polyoma virus. The crystal structure of
a recombinant polyomavirus VP1 pentamer (residues 32-320), in
complex with a branched disialylated hexasaccharide receptor
fragment, extends our understanding of oligosaccharide receptor
recognition (Fig. 1C).
38,39
The model presented here offers a much
more refined view of the interactions that determine carbohydrate
β
