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the structure of the KSHV portal complex present in the KSHV native
capsids (Fig. 5a).
The third related paper, by Cardone
et al.
, presented an averaged
HSV-1 capsid map generated from alignment based on template
matching over the tomograms.
68
It is possible that template matching
introduced model bias, a problem made more severe in this particu-
lar case by the high level of noise present in cryoET tomograms.
Moreover, the inherent missing-wedge problem due to limited tilt
range in cryoET could have introduced structure distortion, which is
quite likely to mislead template matching. This result is in agreement
with the “docking experiments” in the paper published by the same
group.
67
It is noteworthy that the docking was based on an assump-
tion that the portal mass lies outside the capsid shell. This assumption
stands contrary to the observations made in the native KSHV capsid
70
and the chemically treated HSV-1 capsid.
69
Biochemical studies of KSHV particles have been particularly lim-
ited due to their low yield in culture and the consequent difficulty in
viral particle isolation and purification. CryoET reconstructions of
KSHV have provided the first direct evidence for the existence of a
unique vertex or portal in KSHV or any gammaherpesviruses.
70
Indeed, the identification of the KSHV portal by cryoET reconstruc-
tion represents a new, alternative pathway of discovery using structural
data, especially for proteins of lower abundance, when biochemical
data remain scarce.
Capsid and Associated Structures of
Human Herpesviruses
Among the many subviral particles and various enveloped particles pres-
ent at various stages of the herpesvirus lytic replication cycle, the capsid
is the most extensively studied structure to date. The herpesvirus capsid
is particularly suitable for single-particle cryoEM reconstruction, thanks
to the presence of icosahedral symmetry in the capsid shell (except for
the presence of a unique portal vertex), the relative ease of isolation
from the host nucleus, and the capsid shell's structural stability. Even at
a moderate resolution of 20-30 Å, capsid subunits can be observed
