Biology Reference
In-Depth Information
largest. Packaging a “head full” of viral DNA within a capsid has constrained
the maximum and minimum size of herpesvirus genomes.
The β-herpesvirus exhibit relatively lengthy replication cycles, remain sub-
stantially cell associated, and generally do not cross host species barriers. This
subfamily currently includes three genera (Table 1): cytomegaloviruses, murome-
galoviruses and roseoloviruses (Pellett and Roizman 2006). Cytomegaloviruses
include human (HCMV), chimpanzee (CCMV) and rhesus cytomegalovirus
(RhCMV); muromegaloviruses include mouse (MCMV) and rat cytomegalovirus
(RCMV); and the more distantly related roseoloviruses include human herpes
viruses 6A, 6B and 7 (HHV-6A, HHV-6B and HHV-7). The sizes of the β-herpes-
virus genomes that have been sequenced range from approximately 241 kbp for
chimpanzee cytomegalovirus (CCMV) to approximately 145 kbp for the HHV-7
roseolovirus; the human cytomegalovirus (HCMV) genome is approximately
235,000 bp (Table 1).
Genome Organization and cis -Acting Elements
As is true for other herpesviruses, β-herpesvirus genomes are linear when isolated
from virions, and linear HCMV DNA has been shown to contain a single unpaired
base at each end (Tamashiro and Spector 1986). HCMV DNA is replicated by a
rolling circle mechanism to generate multiple tandemly linked copies of the viral
genome. When it is packaged, the catenated DNA is cleaved to generate unit-length
molecules, and the unpaired base at each end facilitates circularization of the
genome at the start of the next round of infection.
The genomes of HCMV and CCMV have a so-called class E organization
(Pellett and Roizman 2006), with two domains that can be inverted relative to each
other, yielding equal amounts of four genomic isomers that can be isolated from
virus particles. The two domains are known as the long and short genome segments
(L and S), and each domain is comprised of a central unique region (U L and U S )
flanked by repeated segments that reside at either the ends of the complete genome
(TR L and TR S ) or internally at the intersection of long and short segments (IR L and
IR S ). Consequently, the HCMV and CCMV genomes have the general organization:
TR L -U L -IR L -IR S -U S -TR S .
The TR L region is comprised of a n and b sequences, the IR L -IR S region contains
b a n c ′ sequences and the TR S regions contains c and a n sequences, where prime
designations signify sequences in reverse orientation relative to sequences without
primes. Thus, the repeats are organized as follows: a n b -U L - b a n c ′-U S - ca n . The terminal
a n sequences can recombine with the internal a′ n sequences, thereby enabling the
isomerization of the HCMV and CCMV genomes. In contrast, RhCMV has a class
F genome with no known terminal repeated sequences, whereas MCMV and
RCMV have class A genomes with terminal but not internal repeats. Consequently,
class A and F genomes do not isomerize.
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