Biology Reference
In-Depth Information
internalized at 34
C, the virus is apparently not transported to lyso-
somes as shown by the lack of viral RNA degradation products after 60
min.
85
This may indicate that HRV14 follows the recycling pathway, or
that it is targeted to other organelles or escapes from the endosomes.
°
Entry of Minor Group HRVs
In contrast to ICAM-1, the receptors of minor group HRVs, LDLR,
LRP and VLDLR, possess one or more clathrin-localization signals
in their cytoplasmic tails.
86
Nevertheless, HRV2 can also be internal-
ized by a clathrin-independent pathway when the clathrin-dependent
route is inhibited by potassium depletion or by overexpression of
non-functional dynamin K44A.
87-89
In the absence of such treatments,
HRV2 may enter entirely via clathrin-coated pits and vesicles.
90
Similar
to the natural ligands of LDLR,
49
HRV2 dissociates from its receptors
at a pH of 6.0.
91
This conclusion is derived from experiments in which
the pH-dependence of HRV2 dissociation from the plasma mem-
brane of HeLa cells was analyzed at 4
C, a condition allowing virus
binding to plasma membrane receptors, but not internalization.
Furthermore, plasma membrane expression of LDLR and LRP is not
altered during continuous HRV2 internalization (unpublished obser-
vations), indicative of receptor recycling. Since early endosomes main-
tain a mildly acidic pH of 6.0, which induces dissociation of HRV2
from its receptor(s), LDLR and LRP presumably recycle through the
PNRC, whereas HRV2 becomes part of the fluid-phase of the endo-
somes and is sorted into ECV (Fig. 5). The virus is then transported
via late endosomes to lysosomes, where it is degraded.
85,92
°
Conversion of Native Virus into Subviral Particles:
Role of Receptors and Low pH
Structural changes of the capsid occur within the endosomal compart-
ments, ultimately resulting in the release of the genomic RNA. It is
believed that native virions first lose, to various degrees, the innermost
capsid protein VP4, resulting in the generation of subviral A-particles
93
;
these are further converted to B-particles after the release of the RNA.
Upon ultracentrifugation, native virions sediment at 150S and subviral
