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cytoplasm that co-localized with MTs (Ogawa-Goto et al. 2003). These capsids
displayed a dense outer layer that likely represents tightly associated tegument
proteins. This compelling study strongly suggests that entering HCMV capsids
and tightly associated tegument proteins travel through the cytoplasm on MTs
toward the nucleus, and that this process is important for viral gene expression and
replication. One of these tightly associated tegument proteins appears to be pp150,
and the recent generation of infectious virus containing a pp150-GFP fusion pro-
tein (Sampaio et al. 2005) should allow for the visualization and quantitation of
capsid transport to the nucleus in live cells.
Additional candidates for HCMV tegument proteins tightly associated with
entering capsids are pUL47 and pUL48. Circumstantial evidence suggests that the
UL47/UL48 protein complex (Bechtel and Shenk 2002) may play significant roles
in the transport of infecting HCMV capsids to the nucleus and/or in the injection of
viral DNA into the nucleus through the nuclear pore complex. The pseudorabiesvi-
rus (PRV) orthologs of pUL47 and pUL48 (pUL37 and pUL36, also called VP1/2,
respectively) also form a complex (Klupp et al. 2002) and, as visualized in live
cells, travel with entering capsids toward the nucleus and accumulate with them at
the nuclear rim (Luxton et al. 2005). The herpes simplex virus type 1 (HSV-1)
orthologs (pUL37 and pUL36, also called VP1/2, respectively) also interact with
each other (Vittone et al. 2005) and may be the tegument proteins required for the
in vitro (and presumably in vivo) transport of viral capsids along MTs (Wolfstein
et al. 2006). Interestingly, a temperature-sensitive mutant in HSV-1 UL36 docks at
the nuclear pore complex during entry but fails to release viral DNA into the
nucleus (Batterson et al. 1983).
Direct evidence of a role for pUL47 and pUL48 in the delivery of viral genomes
to the nucleus also exists. Experiments with an HCMV UL47-null mutant revealed
a decrease in the overall accumulation of the UL48 protein and in its incorporation
into virions (Bechtel and Shenk 2002). Therefore, the UL47-null virus is also hypo-
morphic for pUL48. Upon infection of permissive fibroblasts with a UL47-null
virus, viral immediate early gene expression is delayed, but entry, as assayed by the
delivery of the tegument proteins pp65 and pp71 to the nucleus, appears to be nor-
mal (Bechtel and Shenk 2002). Thus, viruses lacking UL47 have a defect that is
postfusion, but prior to immediate early gene expression. A model in which the
HCMV pUL47/pUL48 complex binds to viral capsids and perhaps microtubule
motors to mediate the delivery of the capsid to the nuclear pore with the subsequent
release of the viral DNA into the nucleus appears to be consistent with the current
data. The pp150 protein may also participate in this process. A similar scenario
likely occurs for PRV and HSV-1.
Many intriguing questions remain about how tegument proteins and DNA-
containing capsids are delivered to nuclear pores, and how the viral genome enters
the nucleus. For example, how does the tegument disassemble before, during or
after entry? There is a clear example of one tegument protein (pp65) that transits
into the nucleus without an intact MT network (Ogawa-Goto et al. 2003), and one,
pp150, that remains tightly associated with the capsid (Sinzger et al. 2000) and
fails to migrate toward the nucleus in the absence of MTs (Ogawa-Goto et al.
2003). The subcellular localization of other tegument proteins including pp71,
