Reactivation can be induced by depletion of nerve growth factor; other commonly used reactivation stimuli have no significant effect.<b>IMPORTANCE</b> Infections by herpes simplex viruses (HSV) cause painful cold sores or genital lesions in many people; less often, they affect the eye or even the brain.
These humoral factors can generally be divided into those which, like RANKL, are tumour necrosis family (TNF) superfamily members and those which are not; the former include TNFα lymphotoxin exhibiting inducible expression and competing with herpes simplex virus glycoprotein D for herpesvirus entry mediator, a receptor expressed by T lymphocytes (LIGHT), a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF); the latter include transforming growth factor beta (TGF-β), interleukin-6 (IL-6), IL-8, IL-11, nerve growth factor (NGF), insulin-like growth factor-I (IGF-I) and IGF-II.
TrkA, the receptor tropomyosin-related kinase for nerve growth factor, is critical not only for the correct spatial and temporal development of sensory neurons during embryogenesis but also for the survival of sensory neurons, the differentiation and apoptosis of neuronal tumors and suppression of latent herpes simplex virus genomes.
In the present study, HEK-293 cells that stably and inducibly produce NGF were further stably transfected with herpes simplex virus-thymidine kinase gene as a suicide gene (hNGF-EcR-293-TK) in order to shut off the NGF secretion and kill the cells upon treatment with ganciclovir (GCV).
The goals of this work were to determine the stability of the expression of the herpes simplex virus type-1 thymidine kinase and the low-affinity receptor for nerve growth factor truncated of its intracellular domain (deltaLNGFR) genes inserted in a murine T lymphoma; in addition, we sought to determine whether a bystander effect (direct or indirect) was present after treatment of the transduced tumor with ganciclovir.