Dataset Information

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells.

ABSTRACT: A global HSV-1 gene repression occurs during latency in sensory neurons where most viral gene transcriptions are suppressed. The molecular mechanisms of gene silencing and how stress factors trigger the reactivation are not well understood. Thyroid hormones are known to be altered due to stress, and with its nuclear receptor impart transcriptional repression or activation depending upon the hormone level. Therefore we hypothesized that triiodothyronine (T3) treatment of infected differentiated neuron like cells would reduce the ability of HSV-1 to produce viral progeny compared to untreated infected cells. Previously we identified putative thyroid hormone receptor elements (TREs) within the promoter regions of HSV-1 thymidine kinase (TK) and other key genes. Searching for a human cell line that can model neuronal HSV-1 infection, we performed HSV-1 infection experiments on differentiated human neuroendocrine cells, LNCaP. Upon androgen deprivation these cells undergo complete differentiation and exhibit neuronal-like morphology and physiology. These cells were readily infected by our HSV-1 recombinant virus, expressing GFP and maintaining many processes iconic of dendritic morphology. Our results demonstrated that differentiated LNCaP cells produced suppressive effects on HSV-1 gene expression and replication compared to its undifferentiated counterpart and T3 treatment has further decreased the viral plaque counts compared to untreated cells. Upon washout of the T3 viral plaque counts were restored, indicating an increase of viral replication. The qRT-PCR experiments using primers for TK showed reduced expression under T3 treatment. ChIP assays using a panel of antibodies for H3 lysine 9 epigenetic marks showed increased repressive marks on the promoter regions of TK. In conclusion we have demonstrated a T3 mediated quiescent infection in differentiated LNCaP cells that has potential to mimic latent infection. In this HSV-1 infection model thyroid hormone treatment caused decreased viral replication, repressed TK expression and increased repressive histone tail marks on the TK promoter.

SUBMITTER: Figliozzi RW

PROVIDER: S-EPMC4252976 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells.

Figliozzi Robert W RW Chen Feng F Balish Matthew M Ajavon Amakoe A Hsia S Victor SV

Journal of the neurological sciences 20140820 1-2

A global HSV-1 gene repression occurs during latency in sensory neurons where most viral gene transcriptions are suppressed. The molecular mechanisms of gene silencing and how stress factors trigger the reactivation are not well understood. Thyroid hormones are known to be altered due to stress, and with its nuclear receptor impart transcriptional repression or activation depending upon the hormone level. Therefore we hypothesized that triiodothyronine (T3) treatment of infected differentiated n ...[more]

PMID: 25175854

Similar Datasets

Project description:BackgroundThyroid stimulating hormone (TSH) suppression therapy after differentiated thyroid carcinoma surgery causes cognitive impairment. However, data on naming difficulties (anomia)-related specific cognitive impairment are lacking.MethodsA prospective cohort study was conducted, in which, patients with differentiated thyroid carcinoma and benign thyroid nodules were given oral L-T4 therapy after surgery, after meeting the criteria of TSH suppression therapy and thyroxine replacement therapy, respectively, the patients were continually given L-T4 therapy for 6 and 12 months, and then, the neuropsychological test was performed.ResultsOf the 255 subjects, 212 cases (83.13%) completed all the tests, including 33 cases in the normal control group (NC group), 110 cases in the TSH suppression therapy group (TS group), and 69 cases in the thyroxine replacement therapy group (TR group). There was no significant difference in background data among the three groups (P > 0.05). The scores of mini-mental state examination, clock drawing test, digit symbol substitution test, personal history, temporal and spatial orientation, digit order relation, visual object recognition, associative learning, and color naming in the TS and TR groups were not significantly different from those in the NC group after 6 and 12 months of L-T4 therapy (P > 0.05); the scores of picture recall, visual recall, comprehension memory, and digit span forward in the TS and TR groups were notably lower than those in the NC group (P < 0.01); the scores of confrontation naming and listing the names in the TS group were significantly lower than those in the NC and TR groups, and the scores decreased with the prolongation of TSH suppression therapy (P < 0.01).ConclusionTSH suppression therapy after differentiated thyroid carcinoma surgery could lead to short-term memory impairment, attention impairment, word selection anomia, and depression, of which, word selection anomia was aggravated with the prolongation of TSH suppression therapy. Therefore, we suggested that optimal TSH goals for individual patients must balance the potential benefit of TSH suppression therapy with the possible harm from subclinical hyperthyroidism especially in low risk differentiated thyroid carcinoma patients (ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT0266532, Registered on 21 June 2016).

Dataset Information

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells.

Publications

Thyroid hormone-dependent epigenetic suppression of herpes simplex virus-1 gene expression and viral replication in differentiated neuroendocrine cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets