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Alternatively, infection of CD34
+
stem cells could, in itself, promote lineage
commitment of the latently infected cell to specific myeloid cell types. Although
there is no direct evidence for this, differences in the cellular transcriptome of
experimentally latently infected GM-Ps compared with uninfected GM-Ps suggest
that such changes in cellular gene expression upon latent infection could, hypo-
thetically, promote lineage commitment of these myeloid progenitor cells
(Slobedman et al. 2004). Thus, whether viral genome carriage in only certain myeloid
cells is a consequence of HCMV initially infecting specific CD34
+
subpopulations
which are already committed to different lineages or is due to the latent infection
itself, promoting lineage commitment to specific myeloid cell types, is unclear, but
both are plausible.
It is clear that a critical determinant of whether the outcome of an infection is
productive or latent is dependent on the regulation of IE gene expression: if repres-
sion of the MIEP prevails, latency will probably be established (Sinclair and
Sissons 1996). However, whether this also involves expression of other specific
viral genes is not clear. As stated previously, experimental latency models have
identified a wide range of viral transcripts which appear to be expressed during
latency. However, many of these are not exclusive to latent infection (Lunetta and
Wiedeman 2000; Bego et al. 2005; Goodrum et al. 2007) and their expression has
not been confirmed in natural latency (Beisser et al. 2001; Goodrum et al. 2002;
Cheung et al. 2006). Consequently, they may simply represent noise from abortive
or productive infection in certain subpopulations of progenitor cell types or they
may represent a class of viral gene products required to establish latent infection
(see Sect. 4, above).
The Maintenance of HCMV Latency
Latency is established within myeloid cells, a cell type with substantial proliferative
capacity (Metcalf 1989). Between two and ten copies (Slobedman and Mocarski
1999) of the HCMV genome are carried in an episomal form in mononuclear cells
in the peripheral blood of healthy seropositive individuals (Bolovan-Fritts et al.
1999). How the viral genome is maintained in these dividing progenitor cells is
unclear. Contrast this with the gamma herpesvirus Epstein-Barr Virus (EBV),
which has a defined latent origin of replication (Yates et al. 1984; Adams 1987) and
encodes a number of latently expressed genes. Some of these viral genes have
defined roles in viral latent genome maintenance in B cells (Leight and Sugden
2000; Young et al. 2000). HCMV does not have similar genes and does not have a
known latent origin of replication. Genome replication does not appear to be due to
any low-level persistence in the cells in which HCMV is carried in vivo. Recently,
Mocarski et al. reported the identification of a segment of genome with proximity
to the IE region of HCMV that appears to be important for carriage of the viral
genome in an experimentally infected GM-Ps (Mocarski et al. 2006). Since the
carriage of viral genomes in these cells occurs without lytic gene expression (Hahn
