Cytomegalovirus and Varicella–zoster Virus Vaccines
161
the largest of all human viruses. The
complete nucleotide sequence has been
determined for both the AD-169 and
Towne laboratory-adapted strains,
and
this sequence contains approximately 200
distinct
open
reading
frames
(ORFs)
capable of coding for approximately 200
distinct polypeptides. In contrast, the VZV
DNA genome is 125 kb in length, and the
complete nucleotide sequence determined
for several strains predicts 71 ORFs for
potential viral polypeptides. As shown
in Fig. 2, herpesviral genomes have the
unusual characteristic of repeated DNA
sequences at one or both ends and at an
internal site (TR and IR), which results in
recombinational inversion of unique long
(U
L
) and/or unique short (U
S
) sequences
during intracellular DNA replication. Each
of the four isomeric forms of the linear
DNA genome for CMV and the two
isomers for VZV can be packaged with
equivalent ef±ciency into new virions and
exhibit similar infectivity. Determination
of the location and nucleotide sequences
of individual genes in the large DNA
genomes of VZV and CMV (Fig. 2) has
permitted detailed structural analysis of
the deduced amino acid sequences for
immunologically important viral proteins.
This has greatly facilitated expression of
these genes into recombinant protein or
inclusion into live-recombinant vaccines.
2.2
Immunogenic Proteins for Eliciting
Neutralizing Antibody
A general principal of viral immunology
is that surface proteins of the virion are
the target antigens for protective antibody
responses. In the case of lipid-enveloped
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0
TR
L
CMV
(230 kb)
VZV
(125 kb)
U
L
U
L
IR
S
TR
S
U
S
IR
L
IR
S
TR
S
U
S
UL32
pp150
UL55
gB
ORF31
gB
ORF37
gH
ORF62
IE62**
ORF63
IE63*
ORF68
gE
UL75
gH
UL83
pp65
UL123
IE1
***
Fig. 2
Structure of the DNA genome for CMV and VZV and location of
genes for important viral antigens. Only one of four possible isomers for
CMV and one of the two possible isomers for VZV are displayed. The top
scale corresponds to genetic map units (0.0–1.0). Open boxes represent
inverted repeat sequences at the ends of the unique long (U
L
) and unique
short (U
S
) genome segments, and arrows indicate the orientation of
coding sequences, which are identiFed by gene number and gene product.
Thes
ing
leanddoub
leasterisksind
icatethepos
itionsofinverted
duplication of
IE62
and
IE63
genes at the right end of the VZV genome.
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