Nuclear domain 10 as preexisting potential replication start sites of herpes simplex virus type-1
Abstract
The herpes simplex virus type 1 (HSV-1) nuclear replication cycle begins at localized sites, but it has remained unclear whether these sites are associated with any defined nuclear structure. We have previously shown that during infection, the HSV-1 immediate-early protein ICP0 dispersed proteins associated with ND10, nuclear sites that contain high concentrations of PML and other potentially regulatory proteins and correspond to the ultrastructurally defined nuclear bodies. Using in situ hybridization and immunohistochemical techniques, we found that ICP0 mutants of HSV-1 replicate in the close proximity with ND10, but increasing replication sites develop away from these nuclear structures. Input wild-type HSV-1 DNA was found preferentially adjacent to ND10 before ICP0 modified these nuclear structures and did not colocalize with ICP8 containing so-called prereplication sites. The sites where HSV-1 can begin replication then need to be redefined as preexisting potential replication sites. Viral RNA was also found associated with ND10 before early protein synthesis (ICP8), suggesting that input virus genomes are deposited at ND10 before they start replication. The deposition of input viral DNA at ND10 is virus gene expression i...Continue Reading
Citations
Herpes simplex virus immediate-early protein ICP0 is targeted by SIAH-1 for proteasomal degradation.
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