Xp. Chen et al., Herpes simplex virus type 1 ICP0 protein does not accumulate in the nucleus of primary neurons in culture, J VIROLOGY, 74(21), 2000, pp. 10132-10141
Infected-cell protein 0 (ICP0), the product of the herpes simplex virus (HS
V) immediate-early (IE) alpha 0 gene, is a promiscuous transactivator of vi
ral early (E) and late (L) gene expression. HSV mutants lacking ICP0 functi
on are severely deficient in viral growth and protein synthesis, particular
ly at low multiplicities of infection. Early in the infectious process in v
itro, ICP0 protein accumulates in distinct domains within the nucleus to fo
rm characteristic structures active in the transcription of viral genes. Ho
wever, following infection of primary trigeminal ganglion cells in vitro wi
th a recombinant HSV mutant that expresses only ICP0, we observed that ICP0
protein accumulated in the characteristic intranuclear distribution only i
n the nuclei of Schwann cells; neurons in the culture did not accumulate IC
P0 despite expression of ICP0 RNA in those cells. The same phenomenon was o
bserved in PC12 cells differentiated to assume a neuronal phenotype, In pri
mary neurons in culture, the amount of ICP0 protein could be increased by p
harmacologic inhibition of calcium-activated protease (calpain) activity or
by inhibition of protein phosphatase 2B (calcineurin), The failure of ICP0
protein to accumulate in the nucleus of neurons suggests that one mechanis
m which may impair efficient replication of the virus in neurons, and thus
favor the establishment of viral latency in those cells, may be found in th
e cell-specific processing of that IE gene product.