160
Cytomegalovirus and Varicella–zoster Virus Vaccines
long-term clinical trial. In seropositive but
immunocompromised individuals, such
as candidates for transplantation
and
immunosuppression, inactivated varicella
virus or recombinant protein subunit vac-
cines may be safer alternatives even though
they are generally less effective in stimu-
lating cytotoxic T cells.
2
Virion Structure and Composition
All of the members of the human her-
pesvirus family have a common structure
for the virus particle, or virion, as shown
in Fig. 1. From the inside to the out-
side, there are four structures: an inner
core containing the viral genetic informa-
tion (DNA genome) associated with viral
protein, a protein shell with icosahedral
symmetry known as an icosahedral cap-
sid, an amorphous layer containing viral
proteins known as the tegument or ma-
trix, and a surface envelope composed
of a cell-derived lipid bilayer and mul-
tiple species of viral glycoprotein. The
single-letter alphabetical nomenclature for
individual envelope glycoproteins is based
upon homology to envelope glycoproteins
of herpes simplex virus-1 (HSV-1). The
envelope is the most fragile component
of the virion, and removal or destruction
of the envelope with detergents or or-
ganic solvents such as ether or chloroform
renders the virion noninfectious. The cor-
responding capsid, tegument/matrix, and
envelope glycoproteins of CMV and VZV
serve similar functions in virus attachment
to cells, intracellular replication, and virus
assembly and egress. However, the corre-
sponding CMV and VZV proteins have
distinct amino acid sequences and can
be distinguished by reactivity with VZV-
speci±c versus CMV-speci±c antibody.
2.1
Viral DNA Genomes and Specifc Gene
Sequences For Recombinant Vaccines
The viral genome for all herpesviruses
is a linear molecule of double-stranded
DNA. This genome encodes all these
virion-associated structural proteins as
well
as
additional
nonstructural
viral
proteins that may function as intracellular
enzymes and regulatory proteins. The
230 kb DNA genome of CMV is among
Lipid bilayer (envelope)
Major glycoproteins:
CMV gB, gH/gL/gO
VZV gE/gI, gB, gH/gL/gO
Tegument/matrix proteins:
CMV pp65, pp150
VZV IE62, IE63
Icosahedral capsid
Genome
=
linear, double-stranded DNA
150
200 nm
±ig. 1
Structure and composition of CMV and VZV virions.
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