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Journal of Virology, November 2000, p. 10132-10141, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Herpes Simplex Virus Type 1 ICP0 Protein Does Not
Accumulate in the Nucleus of Primary Neurons in Culture
Xiao-Ping
Chen,1
Jia
Li,1
Marina
Mata,1,2
James
Goss,1
Darren
Wolfe,3
Joseph C.
Glorioso,3 and
David J.
Fink1,2,3,*
Departments of
Neurology1 and Molecular Genetics and
Biochemistry,3 University of Pittsburgh School
of Medicine, Pittsburgh, Pennsylvania 15213, and VA Medical
Center, Pittsburgh, Pennsylvania 152402
Received 2 May 2000/Accepted 9 August 2000
Infected-cell protein 0 (ICP0), the product of the herpes simplex
virus (HSV) immediate-early (IE)
0 gene, is a promiscuous transactivator of viral early (E) and late (L) gene expression. HSV
mutants lacking ICP0 function are severely deficient in viral growth
and protein synthesis, particularly at low multiplicities of infection.
Early in the infectious process in vitro, ICP0 protein accumulates in
distinct domains within the nucleus to form characteristic structures
active in the transcription of viral genes. However, following
infection of primary trigeminal ganglion cells in vitro with a
recombinant HSV mutant that expresses only ICP0, we observed that ICP0
protein accumulated in the characteristic intranuclear distribution
only in the nuclei of Schwann cells; neurons in the culture did not
accumulate ICP0 despite expression of ICP0 RNA in those cells. The same
phenomenon was observed in PC12 cells differentiated to assume a
neuronal phenotype. In primary neurons in culture, the amount of ICP0
protein could be increased by pharmacologic 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 mechanism 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 the cell-specific processing of that IE gene product.
*
Corresponding author. Mailing address: S-520 BST, 200 Lothrop St., Pittsburgh, PA 15213. Phone: (412) 648-9793. Fax: (412) 648-8081. E-mail: dfink{at}med.pitt.edu.
Journal of Virology, November 2000, p. 10132-10141, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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