Biology Reference
In-Depth Information
Fig. 7.
Potential mechanism of uncoating and genome penetration of the
major (
A, B
) and minor group (
C, D
) HRVs. (
A, B
): Binding of major group
HRVs (e.g. HRV3, 14, 16) to ICAM-1 (shown in green) leads to receptor clus-
tering and therefore internalization of the complex via clathrin-coated vesicles.
The clathrin coat is rapidly lost (within 30 sec). The resulting vesicles (
A
) then
fuse with early endosomes (
B
). The receptor-induced structural alteration results
in externalization of hydrophobic residues. Concomitantly, the endosomal mem-
brane is ruptured and the RNA is released into the cytoplasm (
B
). Given a resi-
dence time of 5 min in early and of 15-20 min in ECV/late endosomes, RNA
penetration can occur from either compartment as a function of time and pH
required for uncoating of the respective serotype. (
C, D
): Minor group viruses
(e.g. HRV2) remain bound to LDLR (grey) in endocytic vesicles that maintain
a pH
6.0 (plasma membrane derived clathrin-coated and non-coated vesicles;
(
C
)). After receptor dissociation at pH
>
6.0 (in early endosomes), the virus is
transferred to endosomal carrier vesicles (ECV). The structural modification is
solely induced by the low pH
≤
5.6 in multivesicular ECV (
D
). The hydropho-
bic N-termini of VP1 together with VP4 might form a pore in the endosomal
membrane through which the RNA is translocated into the cytoplasm. During
this process, ECV remain intact and also maintain their low pH.
≤
