Biology Reference
In-Depth Information
Golgi complex, and is part of the productive infectious route used by
SV40. There is no SV40 in the cell nucleus after a 16-hour infection. 48
It is assumed that SV40 in ER dissociated into VP1-pentamers to
release minichromosome.
There has been suggested that treatment of polyoma virions with
EGTA and dithiothreitol (DTT) resulted in the dissociation of the
virions into a DNA-protein complex and individual structural cap-
somere subunits in vitro . 49,50 It is interesting to presume that this arti-
ficial dissociation partially reflect the actual biological event of SV40
in ER. Recently, a protein disulfide isomerase (PDI)-like protein,
ERp29, exposes the C-terminal arm of polyomavirus VP1 protein,
leading to formation of a hydrophobic particle that binds to a lipid
bilayer; this reaction likely mimics initiation of polyomavirus penetra-
tion across the ER membrane. 51 These results thus identify an ER fac-
tor that mediates membrane penetration of a nonenveloped virus and
suggest that PDI family members are generally involved in ER remod-
eling reactions. Although not essential, the reducing agent DTT and
the calcium-chelator EGTA stimulated the ER-induced polyomavirus
conformational change. It is possible that DTT and EGTA partially
destabilized polyomavirus structure, enabling ERp29 to subsequently
expose VP1's C-terminal arm efficiently. This explanation is supported
by previous biochemical and X-ray structural studies that showed that
disulfide bridges and calcium ions provide critical structural support
for polyomavirus. 2,50 Because the disulfide bond in polyomavirus viri-
ons is in the proximity of the N terminus of VP1, its reduction may
enable ERp29 to also expose the VP1 N terminus. DTT and EGTA
likely mimicked the action of ER reductases (e.g. PDI) and calcium
binding proteins (e.g. calnexin and calreticulin) that would normally
act on the virus. It has been suggested that VP2 and VP3 are involved
in the transport of minichromosome into the nucleus. It has been
shown that VP2 and VP3 nuclear localization signals have important
roles in nuclear transport of minichromosome with importins. 52 VP2
and VP3 NLS were partially exposed outside of the virion in ER, then
after detachment of partially dissociated virion associates with importins
and transport minichromosome into nucleus through nuclear pore com-
plex. It has also been suggested that capsid disassembly within the ER
Search WWH ::




Custom Search