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The tegument is the compartment between the nucleocapsid and
the envelope in herpesviruses and is thus architecturally equivalent to
the matrix protein layer of other enveloped viruses, such as retro-
viruses and rhabdoviruses. Viral proteins in the tegument compart-
ment are the least understood components, partly due to difficulties
in isolating them. They play important functional roles in multiple
aspects of the viral lifecycle, including capsid transport to the nucleus
and virion assembly and egress. 53,55 The proximity of the tegument
proteins to the surface of the viral capsid suggests that they may also
be involved in modulating the interactions between viral capsids and
the host cellular proteins upon entry into the cell. 56,57 In HSV-1, the
tegument is asymmetrical and may contain actin-like filamentous
substructures. 47
Although there are several tegument proteins that are conserved
in all herpesviruses, a large proportion of the tegument layer is appar-
ently composed of proteins unique to each subfamily (Table 2). 58,59
The existence of distinct tegument layers among different subfamilies
of herpesviruses (Fig. 4) has important biological implications in her-
pesvirus assembly and egress. Our structures of the betaherpesvirus
tegument 60 and gammaherpesvirus tegument 61 clearly point to a diver-
gence from that of HSV-1, 2 which is likely the result of divergence in
the protein composition of the tegument. While inner tegument pro-
teins in herpesviruses may be involved in essential processes in virion
morphogenesis, such as capsid transport into and within the cytoplasm,
outer tegument proteins are involved in modulating the host cell
environment in the immediate-early phase of infection. 62,63 It is pos-
sible that during the course of herpesvirus evolution, some modulat-
ing proteins gained signals, allowing incorporation into the virion
particle in a manner that did not disrupt the relatively conserved
processes of capsid assembly, egress from the nucleus, and transloca-
tion to the site of virion assembly in the cytoplasm. The outer tegu-
ment layer is thus more divergent not only in structure, but also in its
composition and function of its constituent proteins.
The organization and structure of the inner, or capsid-associated,
tegument proteins varies greatly among herpesviruses across the her-
pesvirus subfamilies. Zhou et al. reconstructed to 20 Å the HSV-1
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