Restriction of multiplication of herpes simplex virus type 1 in a myoepithelial cell line derived from human minor salivary gland

AbstractWe tested the hypothesis that gene transfer using recombinant adenovirus vectors (RAds) expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) might offer an alternative therapeutic approach for the treatment of pituitary prolactinomas that do not respond to classical treatment strategies. HSV1-TK converts the prodrug ganciclovir (GCV) to GCV monophosphate, which is in turn further phosphorylated by cellular kinases to GCV triphosphate, which is toxic to proliferating cells. One attractive feature of this system is the bystander effect, whereby untransduced cells are also killed. Our results show that RAd/HSV1-TK in the presence of GCV is nontoxic for the normal anterior pituitary (AP) gland in vitro, but causes cell death in the pituitary tumor cell lines GH3, a PRL/GH-secreting cell line, and AtT20, a corticotrophic cell line. We have used sulpiride- and oestrogen-induced lactotroph hyperplasia within the rat AP gland as an in vivo animal model. Intrapituitary infection of rats bearing oestrogen-induced lactotroph hyperplasia, with RAd/HSV1-TK and subsequent treatment with GCV, decreases plasma PRL levels and reduces the mass of the pituitary gland. More so, there were no deleterious effects on circulating levels of other AP hormones, suggesting that the treatment was nontoxic to the AP gland in situ. In summary, our results show that suicide gene therapy using the HSV1-TK transgene could be further developed as a useful treatment to complement current therapies for prolactinomas.

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The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line

Virology Journal ◽

10.1186/1743-422x-11-125 ◽

2014 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Aaro Turunen ◽

Veijo Hukkanen ◽

Michaela Nygårdas ◽

Jarmo Kulmala ◽

Stina Syrjänen

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Cell Line ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Combined Effects ◽

Simplex Virus

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Human Neuron-Committed Teratocarcinoma NT2 Cell Line Has Abnormal ND10 Structures and Is Poorly Infected by Herpes Simplex Virus Type 1

Journal of Virology ◽

10.1128/jvi.75.8.3819-3831.2001 ◽

2001 ◽

Vol 75 (8) ◽

pp. 3819-3831 ◽

Cited By ~ 14

Author(s):

Wei-Li Hsu ◽

Roger D. Everett

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Cell Line ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Nuclear Bodies ◽

Simplex Virus ◽

Nt2 Cells ◽

Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP0 stimulates the initiation of lytic infection and reactivation from quiescence in human fibroblast cells. These functions correlate with its ability to localize to and disrupt centromeres and specific subnuclear structures known as ND10, PML nuclear bodies, or promyelocytic oncogenic domains. Since the natural site of herpesvirus latency is in neurons, we investigated the status of ND10 and centromeres in uninfected and infected human cells with neuronal characteristics. We found that NT2 cells, a neuronally committed human teratocarcinoma cell line, have abnormal ND10 characterized by low expression of the major ND10 component PML and no detectable expression of another major ND10 antigen, Sp100. In addition, PML is less extensively modified by the ubiquitin-like protein SUMO-1 in NT2 cells compared to fibroblasts. After treatment with retinoic acid, NT2 cells differentiate into neuron-like hNT cells which express very high levels of both PML and Sp100. Infection of both NT2 and hNT cells by HSV-1 was poor compared to human fibroblasts, and after low-multiplicity infection yields of virus were reduced by 2 to 3 orders of magnitude. ICP0-deficient mutants were also disabled in the neuron-related cell lines, and cells quiescently infected with an ICP0-null virus could be established. These results correlated with less-efficient disruption of ND10 and centromeres induced by ICP0 in NT2 and hNT cells. Furthermore, the ability of ICP0 to activate gene expression in transfection assays in NT2 cells was poor compared to Vero cells. These results suggest that a contributory factor in the reduced HSV-1 replication in the neuron-related cells is inefficient ICP0 function; it is possible that this is pertinent to the establishment of latent infection in neurons in vivo.

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