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possesses a pocket factor, a similar but only additive effect was
observed. These data agree with the in vivo findings that low endoso-
mal pH and the receptor act in concert in viral uncoating, similarly
depending on the serotype. 104 Consequently, raising the endosomal
pH to neutrality by lysosomotropic agents or V-ATPase inhibitors
completely blocks infection of HRV16, but not of HRV3. For HRV14,
the serotype with intermediate stability, the results are conflicting; this
might be due to partial occupancy of the pocket. 104,109,110 Irrespective
of the serotype, infection only occurs above 26
°
C. 111
Conversion of Major Group HRVs In Vivo
Given the lack of lysosomal degradation of HRV14 85
when internal-
ized at 34
C, the virus might use compartments of the recycling
pathway for conformational change and uncoating. Nevertheless, at
this temperature, essentially no virus was found in the endosomes by
immunofluorescence microscopy and subcellular fractionation.
However, at 20
°
C, where the virus remains in its native conforma-
tion, HRV14 was localized in early and late endosomes. 84 Thus, the
structural alteration and uncoating may occur in these compartments.
HRV3 and HRV14 can infect HeLa cells in the presence of
bafilomycin. 104,109 Since this drug arrests cargo en route to lysosomes
in early endosomes, at least these particular serotypes can undergo the
receptor-catalyzed modification and uncoating in early endosomes
(Fig. 5). As to which endosomal subcompartment the structural mod-
ification of the distinct major group serotypes will take place in, will
depend on the time post infection and the pH required for this
process. Since transit through the early endosomes is rapid (2-5 min)
but residence in ECV/late endosomes amounts to 10-20 min, 70,73 the
structural alteration most likely occurs in late compartments.
°
Conversion of Minor Group HRVs In Vitro
For HRV2, and presumably for the other minor group viruses, the
in vitro conversion to subviral particles (mainly A-particles) exhibits a
steep pH dependence that is unaffected by the presence of the cellular
receptors. The kinetics of this modification can by analyzed using an
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