Biology Reference
In-Depth Information
mice,
35
many open questions about the receptor function still remain.
Due to the different interaction mechanism of
integrin and
EV1 when compared to natural ligands, it is not clear whether virus
binding can trigger a similar conformational change in the
α 2β 1
2I domain.
If not, there may be neither conformational changes in the
α
subunit
nor separation of the intracellular domains. Thus, after virus binding,
the integrin signaling might be solely due to receptor clustering. A
detailed structure-based analysis of
β
α 2β 1
function after EV1 binding
would clarify these events.
We have shown that EV1 can be found on cell surfaces in struc-
tures resembling caveolae and later inside the cells in caveosomes.
10
However, it is not clear how many different entry routes EV1 can uti-
lize. Furthermore, the exact timing and the mechanisms of viral
uncoating and the release of the RNA genome are currently unknown.
We have preliminary evidence that EV1 may also be engulfed in large
macropinosome-like vesicular structures that very quickly fuse with the
pre-existing caveosomes (Karjalainen
et al
., unpublished). This would at
least partly explain the different timing and routing of EV1 to the
caveosomes when compared to SV40. The fluorescence
in situ
hybridization assay showed that viral RNA is present together with the
capsid proteins in the caveosomes almost until the initiation of viral
replication. Further studies on the molecular details of the EV1 entry
process will most probably shed new light on the complexity of cellular
entry pathways used by microbial pathogens and physiological ligands.
References
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parechovirus 1.
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75
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3. Roivainen M, Piirainen L, Hovi T,
et al
. (1994) Entry of coxsackievirus
A9 into host cells: specific interactions with alpha v beta 3 integrin, the
vitronectin receptor.
Virology
203
(2): 357-365.
4. Verdaguer N, Mateu MG, Andreu D,
et al
. (1995) Structure of the
major antigenic loop of foot-and-mouth disease virus complexed with a
