Biology Reference
In-Depth Information
The representation in Fig. 3 also demonstrates that the contact
areas in the V23/HRV2 complex are much smaller than those of the
ICAM-1/HRV16 complex. However, taking into consideration
simultaneous binding of more than one or even five VLDLR modules
contributed from the same protein, the contact area between the
minor group receptor and HRV2 even exceeds that of the major
group receptor and HRV16. Multi-module binding was definitely
demonstrated by the analytical separation of complexes between
HRV2 and an artificial pentamer of V3 fused to maltose binding pro-
tein (MBP-V33333). Capillary electrophoresis resolved peaks corre-
sponding to virus carrying between zero and 12 receptor molecules,
indicating that the pentamers attach to the 12 vertices of the virus,
most probably involving all five modules. This view is also supported
by the tremendous increase in avidity with the number of modules
present in the recombinant molecule.
60,60a
HRV Entry: Endocytic Pathways
and Selective Inhibitors
For infection to occur, virus, subviral particles, or the viral genome has
to enter the host cell. HRVs enter by receptor-mediated endocytosis
and, more importantly, are dependent on endocytosis for infection (see
below). Consequently, structural modifications of the viral capsid, as
required for RNA release and penetration into the cytoplasm, occur
from endocytic compartments. Since endosomal subcompartments
maintain different internal environments, it is important to define the
respective endosome population where these events take place. The
mechanism of rhinovirus entry, uncoating, and infection has been stud-
ied predominantly in HeLa cells, which express ICAM-1 as well as
LDLR, LRP, and VLDR; furthermore, in these cells almost all HRV
serotypes replicate to high titers. Due to the difficulty of growing pri-
mary airway epithelial cells, the main site of HRV replication in humans,
few studies have been carried out in this system. A main drawback of
using HeLa cells is their lack of forming polarized monolayers on per-
meable filters despite their being derived from a cervix carcinoma; this
precludes investigations of vectorial uptake or release of the virus.
