Biology Reference
In-Depth Information
The procapsid can be assembled
in vitro
from capsid and scaffold-
ing proteins in the absence of the viral protease.
24
Protease-minus pro-
capsids can spontaneously rearrange into a large-cored, angular
particle resembling the B-capsid, but these large-cored particles do not
encapsidate DNA or become mature virions.
20,21,25
Cells infected with
a temperature-sensitive, protease-minus HSV-1 mutant produce cap-
sids that disassemble at the non-permissive temperature of 0°C, simi-
lar to the
in vitro
-assembled procapsids.
20
However, these capsids
remain unstable at the permissive temperature and do not mature
unless protease activity is restored.
20
The structures of the tempera-
ture-sensitive mutant, protease-minus mutant and
in vitro-
assembled
capsids (Fig. 2) are all similarly porous and spherical compared to that
of the wild-type A-capsid. These experiments illustrate the importance
of protease cleavage in the herpesvirus capsid assembly and confirm
that the procapsid is the precursor of the angular capsid. In fact, the
interactions between the scaffolding protein (also known as assembly
protein, or AP), major capsid protein (MCP), and viral protease have
been explored as targets for antiviral drug design in herpesviruses.
26-30
Further maturation of the capsids into infectious virions remains a
controversial issue. One school of thought is that the capsids acquire
their envelope from the inner nuclear membrane, process the envelope
glycoproteins
in situ
and bud from the cell surface via the secretory
pathway. However, new evidence suggests that HSV-1 capsids acquire
their inner tegument proteins at or near the inner nuclear membrane
and are enveloped temporarily, then fuse with the outer nuclear mem-
brane to release tegumented capsids into the cytoplasm as illustrated in
to the nuclear pore to eject viral DNA into the nucleus, where DNA replica-
tion and RNA transcription occur. Viral proteins are translated in cytoplasm
in stages and some are transported into the nucleus, where capsid assembly
takes place. Spherical procapsids, which contain a ring of scaffolding proteins,
are first assembled first. Spontaneous angularization coupled with DNA pack-
aging lead to the formation of A, B, and C capsids. These capsids acquire their
inner and outer tegument proteins at or near the nuclear membranes,
enveloped, de-enveloped, and re-enveloped through the cellular excretion
apparatus. Enveloped particles are released through exocytosis.
