Biology Reference
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part of the expanding prereplication domain and viral genomes are present at the
outside of this domain. Prereplication domains apparently become the replication
compartments many hours later when they appear hollowed out (Fig. 1f). More
than a decade after the first observation that viruses transcribe predominantly at
ND10, it remains unclear what advantage the virus gains by dispersing ND10-
associated proteins. Is it possible that the questions asked are not relevant and that
transcription at ND10, and ultimately replication where ND10 had been present,
is simply a consequence of various layers of interactions, none of them simply
representing either advantages for the virus or defense mechanisms of the host.
Clearly though, those domains focus our mind on the activities that take place in
these microenvironments.
Because of the limited resolving power of light microscopy, we still do not know
the precise location of transcribing viral genomes relative to ND10 beyond 300 nm
resolution, a huge molecular gap. This is important, because it could mean the virus
has become part of ND10, where its interaction with a solid interface would have
the same mechanistic relevance as recently argued for genes with matrix elements
(Kumar et al. 2007). The viral genome may be localizing at the ND10 interface
within the interchromosomal space, i.e., randomly localizing in the limited inter-
chromosomal space where ND10 also resides. However, the observations that viral
transcription occurs at ND10, that IE1 disperses ND10-associated proteins, and that
interferon induces ND10-associated proteins suggest that the association of viral
transcription and ND10 is causal rather than casual. To understand this relationship
better, we may have to reconstruct the evolutionary balance achieved by a multitude
of interactions, each modifying others.
Are ND10 Really the Start Sites of CMV Transcription?
The static images obtained from fixed material 3 h p.i., certainly suggest as much.
However, the lateral infection sequence employed for HSV1 (infection from a
neighboring cell in the same culture flask plane) indicates that the ND10-associated
proteins leave their initial segregated state and move to the viral genomes (Everett
and Murray 2005). According to this scenario, new aggregates of ND10-associated
proteins form on the virus genome and even prevent the virus genome from moving
into the center of the nucleus. Our early observations for HSV1 and HCMV then
come from the infection and nuclear pore penetration on the large upper surface of
the nuclei, thus requiring a short migration downward to preexisting ND10 (or a
short migration of ND10-associated proteins to the virus). We have shown that for-
eign DNA/foreign protein complexes of bacterial or viral origin attract ND10-
associated proteins whether introduced into cells by infection or transfection (Tang
et al. 2000, 2003). Reiterated HPV11 origins of replication plus the origin binding
protein E2 or integrated bacterial reiterated operon sequences plus GFP-labeled
LacI repressor protein attracted ND10-associated proteins (Tang et al. 2001).
Foreign DNA alone did not. One interesting finding was that foreign DNA/foreign
