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

Abstract

During infection with herpes simplex virus type 1 (HSV-1) the activity of tyrosine hydroxylase (TH) in PC12 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.

Dopamine Metabolism in Hypoxanthine‐Guanine Phosphoribosyltransferase‐Deficient Variants of PC12 Cells

“…Infection by Herpes simplex virus type I has been reported to depress tyrosine hydroxylase activity in PC12 (Rubenstein et al, 1985). We have found that, in at least five of the six HPRT-deficient variants, transformation with HPRT retrovirus had no adverse effects on dopamine metabolism.…”

Replication of lymphocytic choriomeningitis virus is restricted in terminally differentiated neurons

“…These cells can be induced to undergo morphological and physiological differentiation, characterized by a lack of cell division, extension of functional processes, and expression of a variety of neuronal cell-specific markers, following exposure to low doses of nerve growth factor (NGF) (25,26). It has been previously reported that NGF differentiation of PC12 cells persistently infected with herpes simplex virus (HSV) type I delays the transition from early to late HSV polypeptide synthesis (13), while other groups have shown that HSV infection of differentiated PC12 cells leads to transient decreases in levels of enzymes involved in acetylcholine metabolism (54,55).…”