Biology Reference
In-Depth Information
HRV2 conformation-specific monoclonal antibody (2G2) that
detects C-antigenic but not native virions. While essentially no C-
antigenic particles are observed at pH 5.8, 50% conversion is seen at
pH 5.6, and all virions are converted to C-antigen below pH
≤
5.4.
28,91
The conversion is virtually independent of the temperature
within a range of 4
°
C to 34
°
C.
Conversion of Minor Group HRVs In Vivo
In vivo
, formation of subviral particles and infection of HRV2 are solely
low pH dependent as they are blocked when the endosomal pH is
raised to neutrality and take place even when antibody-complexed virus
is internalized via Fc-receptors.
91,112
Furthermore, the structural alteration
is temperature-independent, provided that the virus is still routed into
compartments that maintain a pH below the threshold (pH
5.6) for
the conformational modification (ECV, late endosomes; above 16
≤
C).
92
The products of the conversion, C-antigenic subviral particles, are par-
tially recycled into the medium (“eluted particles”).
To define the compartment where the conformational change of
HRV2 occurs, we have taken advantage of various reagents known to
affect distinct endocytic transport steps (see above).
70,84,92
In the pres-
ence of nocodazole, HRV2 accumulated in ECV. Nevertheless, the
pH-dependent conformational change, recycling of C-antigenic par-
ticles, and infectivity were unaffected, but lysosomal degradation was
prevented. Therefore, (1) ECV and late endosomes have a pH < 5.6
in HeLa cells as they induce the conformational modification of the
virus; (2) recycling of C-antigenic (“eluted”) viral particles can occur
from ECV; and (3) uncoating takes place in ECV. This is in agree-
ment with virus-receptor dissociation in mildly acidic early endosomes
and the conformational modification occurring subsequently in more
acidic EVC (Fig. 5).
°
Mechanism of Genome Uncoating: How is the Viral
RNA Delivered into the Cytoplasm?
A crucial step in the virus entry pathway is membrane penetration/
uncoating of the viral genome to allow for subsequent virus replication.
