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Alteration of tyrosine hydroxylase activity in PC12 cells infected with herpes simplex virus type 1

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Summary

During infection with herpes simplex virus type 1 (HSV-1) the activity of tyrosine hydroxylase (TH) in PC 12 pheochromocytoma cells was initially depressed reaching a nadir at 6 hours post-inoculation, but recovered rapidly with a return to baseline activity by 8 to 9 hours post-inoculation. Subsequently, TH activity again fell with a second more variable rise in activity occurring at 24 hours post-inoculation. Studies with metabolic inhibitors and 2 temperature-sensitive viral mutants indicated that these alterations of TH activity were dissociated from morphological cytopathology and likely required expression of “late” viral gene products. Immunotitration using anti-TH antibody suggested that early depression of TH activity resulted principally from loss of enzyme protein rather than simple enzyme inactivation, and that reconstitution of activity at 9 hours was related to augmented enzyme synthesis. These observations illustrate the complexity of perturbed cellular metabolism during HSV-1 infection and suggest involvement of two unexpected processes: alteration of a specialized cell function as a result of viral genes expressed late in the replicative cycle, and augmented synthesis of a cell-coded gene product during the course of infection.

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Author notes

  1. R. Rubenstein

    Present address: Department of Virology, N.Y. State Institute for Basic Research in Developmental Disabilities, Staten Island, N.Y., U.S.A.

Authors and Affiliations

  1. George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, U.S.A.

    R. Rubenstein, R. W. Price & T. Joh

  2. Laboratory of Neurobiology, Department of Neurology, Cornell University Medical College, New York, U.S.A.

    T. Joh

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Rubenstein, R., Price, R.W. & Joh, T. Alteration of tyrosine hydroxylase activity in PC12 cells infected with herpes simplex virus type 1. Archives of Virology 83, 65–82 (1985). https://doi.org/10.1007/BF01310965

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  • DOI: https://doi.org/10.1007/BF01310965

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