Biology Reference
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number of HCMV gene products that contribute differentially to the replication
success of the virus in different cell types (Dunn et al. 2003). Thus, HCMV miRNA
expression might also be expected to vary in different cell types.
We have examined HCMV miRNA expression in multiple, clinically relevant
cell types (Dunn et al. 2005). These cell types were of epithelial, microglial, and
fibroblast origin. We found that at least in these three cell types, all of the
HCMV miRNAs tested were expressed (Dunn et al. 2005). Generally, all HCMV
miRNA examined were found to be expressed among all the cell types tested.
Qualitatively, expression levels of individual HCMV miRNAs did vary between
cell types. Specifically, they appeared to be expressed most highly in an astro-
glial cell line. In infected retinal pigment epithelial cell lines, viral miRNA
expression appeared to be the lowest among the cell lines examined. Whether
this was due to differential susceptibility of these cell types to viral infection, or
in fact a result of cell type-specific differential HCMV miRNA expression is
under investigation.
To aid in extending the discussion of tissue-specific expression of herpes virus
miRNAs, interesting data have been recently reported concerning the tissue-
specific control of viral miRNA expression in EBV. As noted above, EBV has been
found to express at least 17 miRNAs. These miRNAs are encoded in two distinct
clusters, denoted
BART
and
BHRF1
. While miRNAs derived from the
BART
cluster
were detected in all cell lines studied, they were expressed at much higher levels in
epithelial cells (Cai et al. 2006). In contrast, the
BHRF1
miRNAs were expressed
predominantly in B cells exhibiting stage III EBV latency (Cai et al. 2006). Finally,
it was shown that gastric carcinomas harboring EBV expressed the BART miRNA
cluster but not the BHRF1 miRNAs (Kim do et al. 2007). Presently, however, it is
not clear what role if any the EBV miRNAs play in different cell types and at dif-
ferent stages of viral infection. The impact of specific EBV-encoded miRNAs in
infection awaits interference studies, miRNA target identification and analysis of
recombinant virus deficient in one or more viral miRNAs.
Prior to the discovery of the MHV68 miRNAs, Stewart and colleagues exam-
ined the growth phenotype of a naturally occurring MHV68 variant, MHV-76
(Macrae et al. 2001). MHV76 was isolated from the yellow necked wood mouse
(Blaskovic et al. 1980). MHV76 is identical to MHV68 except for a deletion of
approximately 10 kbp of genomic DNA from the left end of the unique region
(Macrae et al. 2001). This region includes four genes (M1-M4) and all nine
MHV68 miRNAs. Identical growth of MHV68 and MHV76 were observed
in vitro. However, in vivo growth phenotypes were distinguishable, most notably
by a decrease in MHV76 pathogenicity in the spleen and more rapid clearance
from the lung (Macrae et al. 2001; Clambey et al. 2002). It is difficult to ascribe
the MHV76 in vivo growth to the loss of miRNA and analysis is confounded by
the absence of four genes also found in the deleted region. Viruses with deletions
in either M2, M3 or M4 were shown to have similar in vivo growth phenotypes
(Parry et al. 2000; van Berkel et al. 2000; Jacoby et al. 2002; Geere et al. 2006).
Nevertheless, it is interesting that a naturally occurring variant of MHV68, which
is lacking the nine MHV68 miRNAs, exists.
