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Effects of thyroid hormone on HSV-1 gene regulation: implications in the control of viral latency and reactivation

Cell & Bioscience volume 1, Article number: 24 (2011) Cite this article

Abstract

Thyroid hormone (TH) is involved in many biological functions such as animal development, cell differentiation, etc. Variation and/or disruption of plasma TH level often led to abnormalities and physiological disorders. TH exerts the effects through its nuclear receptors (TR). Literature showed that procedures resulted in TH alteration also linked to reactivation of several viruses including Herpes Simplex Virus Type -1 (HSV-1). Bioinformatic analyses revealed a number of putative TH responsive elements (TRE) located in the critical regulatory regions of HSV-1 genes such as thymidine kinase (TK), latency associated transcript (LAT), etc. Studies using neuronal cell lines have provided evidences demonstrating that liganded TR regulated viral gene expression via chromatin modification and controlled viral replication. The removal of TH reversed the inhibition and induced the viral replication previously blocked by TH. These results suggest that TH may have implication to participate in the control of reactivation during HSV-1 latency.

1. Thyroid Hormone Overview

Thyroid hormone (TH or T3) contributes to numerous crucial physiological processes ranging from animal development, proliferation, differentiation, apoptosis, etc [1]. Aberration due to the lack of TH led to disorders such as the goiter (thyroid gland enlargement) and cretinism (a type of severe mental retardation) [2]. TH deficiency may result from the shortage of iodine (essential for TH biosynthesis), thyroidectomy, diseases, or inherited defects, etc. In humans, developmental defects because of TH deficiency can be treated by TH replacement at appropriate time frame [3].

2. Transcriptional regulation by TR

TH is vital for the normal functions of many organs and exert its ability through the nuclear receptor [1]. Two TR genes (TRα and TRß) were identified in vertebrates and both exhibit strong binding to their ligand TH [4–7]. They are members of nuclear hormone receptor super-family [8–10]. Although recent discovery suggested non-genomic action, TRs primarily produce their activity by binding to TH response element (TRE) and regulating transcription in nucleus through the status of TH [11]. TRE is a short DNA sequence located within the promoter of a TH-response gene. The most common TRE sequence is a pair of direct repeats separated by four nucleotides (DR4), indicating that the correspondent receptors bound as a dimer [12]. This TRE is also described as positive TRE since transcription activated by TH requires the interaction of liganded TRs to the DR4-TRE within the promoter of TH-response genes, most likely as heterodimers with RXRs (9-cis retinoic acid X receptors). TR/RXR heterodimers display constitutive interaction to DR4-TRE in chromatin context regardless the status of TH [13]. In the absence of TH, they inhibit the gene expression and the inhibition can be reversed when TH is available for binding to the receptors [13]. TR controls gene expression by recruiting cofactors to the vicinity of promoters. The corepressors are preferentially recruited by unliganded TR while the coactivators are enriched at the promoter via liganded TR [13]. The characterization indicated that corepressors such as SMRT, N-CoR, etc establish complexes with histone deacetylases (HDACs) to facilitate hypoacetylation. This process eliminates those acetyl groups on histone tail, increases the positive charge of nucleosomes, and enhances the interaction between the histones and DNA backbone. As a result, it promotes the chromatin binding and condenses DNA structure, therefore preventing transcription [14]. On the contrary, many coactivators (e.g. SRC-1, CBP/p300) are histone acetyltransferases (HATs) and induce transcription by reversing the previous process [14].

3. Herpes Simplex viruses (HSV) and diseases

HSV is one of the most common causes of infectious disease in humans [15]. This virus contains two distinct types, HSV-1 and HSV-2. Their genomes demonstrate approximately 50% homology. Diseases caused by HSV-1 infection appear frequently [16]. It happens to children about 3 to 5 years old and lasts 5 to 12 days [17]. After the initial infection, the virus may establish latency in the trigeminal ganglia. Reactivation usually occurs over the anterior mucosa, lips or perioral area of face called cold sores or fever blisters [18]. About 10% of viral encephalitis resulted from herpes virus [19]. The factors leading to HSV encephalitis are unknown although a study suggested that latent virus reactivation in the trigeminal ganglia and prolonged lytic infection in the temporal-parietal area of the brain may play a role [20]. Other major clinical syndromes include cornea infection (herpes keratitis) [21], infection of finger and nail (herpetic whitlow) [22], herpes dermatitis [23], and genital HSV infection [24].

4. The genome of HSV-1 and gene expression

a. Genome

HSV-1 has a linear double-stranded DNA genome. The genome contains approximately 80-85 genes and is about 152 kbp long. The G+C content of HSV-1 genome is approximately 68% [25]. It includes two components, designated as L (long) and S (short). Both L and S contain unique sequences, designated as UL and US, and each of them is bracketed by inverted repeats. The L and S of HSV-1 can invert with respect to one another, yielding four linear isomers. The isomers are defined as P (prototype), IL (inversion of the L component), IS (inversion of the S component), ISL (inversion of S and L) [26].

b. Characterization of gene expression

Gene expression of HSV-1 is tightly regulated in a cascade fashion. The three temporal classes of genes are designated immediate-early (α), early (β) and late (γ) genes [27]. There are five α genes and their products are often named Infected Cell Protein (ICP), designated ICP0, ICP4, ICP22, ICP27, and ICP47. All of these proteins have regulatory functions except ICP47, which inhibits major histocompatibility complex class I antigen presentation [28, 29]. The α genes are defined by the presence of the sequence 5'-TAATGARATT-3' (the cis element for induction of α genes by VP16) upstream of the cap site [30]. VP16 interacts with cellular factors, including the protein Oct-1, a homeobox protein, to activate viral α gene transcription in trans [31]. The expression of β genes requires the expression of α genes [32].

5. HSV-1 latency, reactivation, and its regulation by TH

a. Latency and reactivation

HSV-1 establishes latent infections in peripheral nerve ganglia following primary infection in the cells of mucosal membranes or skin [33]. Latent infection is maintained lifelong in the human host. The virus may reactivate from time to time and infectious virus enters peripheral tissues by axonal transport causing recurrent disease or subclinical virus shedding [34]. Latent virus may be reactivated after local or systemic stimuli such as injury to tissues innervated by neurons harboring latent virus, or by emotional or physical stress [35, 36]. During latency, the viral transcription is restricted to a region within the long terminal and internal repeats and the transcripts are designated as "LATs" (Latency Associated Transcripts) [37]. The molecular functions of LAT during latency and reactivation are elusive and the specific roles in gene regulation are not exactly understood. Some suggested that LATs produced anti-apoptotic effects [38]. In neuronal cells, LAT was shown to reduce viral gene expression and replication during productive infection [39]. In vivo, LAT mutant virus enhanced gene expression in sensory neurons during lytic and latent infection [40]. Additional report showed that LAT augments transcriptions of several lytic genes during the latent stage in rabbits [41]. Since they are the only major transcripts produced in significant amounts during latency, the LATs were suggested to play a role in establishing, maintaining, or reactivating latency [42].

During reactivation, LAT gene decreased and was shown to be associated with repressive histones [43]. Transcripts of ICP0, on the other hand, accumulated and the histones around its promoter became acetylated [43]. These results suggested the roles of LAT and ICP0 during the initial stage of reactivation. As for the viral gene expression profile in neurons during reactivation, it was suggested to follow the paradigm of α to β to γ cascade and viral DNA replication occurred after α synthesis, similar to the lytic cycle. However, other reports challenge this view by suggesting different sequence. For example, studies showed that TK-minus mutant exhibited greatly reduced α and β expression during reactivation [44, 45]. These observations were further supported by the finding that TK, a β gene, was detected before α gene expression using explants reactivation model [46]. In addition, viral replication is required for efficient α and β expression in neuron during reactivation [47]. Together, these studies emphasized the importance of TK and viral DNA synthesis during reactivation. Since TK is required to provide dNTP for viral replication in resting cells such as neurons, it is likely that TK may play a critical role to stimulate viral DNA synthesis and α gene expression to promote reactivation.

b. Role of TH on HSV-1 reactivation

The impacts of TH on virus-mediated pathophysiology was discussed but not extensively studied. Low serum thyroxine and other hormone imbalance due to hypothalamic-hypopituitarism were associated with viral meningo-encephalitis and related complication [48]. Effects of TH on AIDS (Acquired Immuno-Deficiency Syndrome) and ARC (AIDS-Related Complex) were investigated and the results suggest that TH may affect disease development and progression [49]. At present, the molecular basis of the HSV-1 latency/reactivation is not extensively understood. In particular, it is not known why virtually the entire HSV genome is transcriptionally silent, with the exception of the LAT region. It is not entirely clear how the latent virus initiates gene expression/replication upon reactivation. Recent studies suggested that TH and TRs played roles on HSV gene silencing/activation and DNA replication during latency/reactivation [50, 51]. There are reasons to hypothesize that the status of TH and its interaction with TRs modulate chromatin and exert functions in HSV-1 latency and reactivation. 1. TR is present in ganglia neurons [52, 53]. 2. TH can affect different biological processes involved in the survival, differentiation, maturation of neurons [54]. 3. TH and nerve growth factor enhanced neurite outgrowth, and regulate the expression of dynein, a protein that is involved in axonal transport (important for virus movement), in ganlia neurons [55]. There is no direct, controlled clinical study regarding the effect of TH on HSV-1 reactivation although alteration of corticosteroid has been linked to HSV-1 reactivation [56, 57]. A case study showed that a patient with myxedema coma under corticosteroid treatment developed herpes simplex encephalitis with extremely low thyroxine level less than 5.2 nmol/L (normal range 12-30 nmol/L) [58]. In addition, literature indicated that many factors, such as stress, febrile diseases, trauma, surgery, radiotherapy, etc, triggering HSV-1 reactivation also altered thyroid hormone level (Table 1).

Table 1 Comparison between triggering factors of HSV-1 reactivation and thyroid hormone alteration
Full size table

This table is intended to provide connection between variation of TH level and HSV-1 reactivation. For example, whole body hyperthermia was reported to reduce the level of serum TH by 50%, probably due to the suppression of thyroid stimulating hormone release, monodeiodination alteration of T4 from TH to reverse T3, and enhanced TH clearance [76]. Importantly, hyperthermia is regularly used by laboratories to trigger HSV-1 reactivation in the mouse latency model [72]. In addition, brain injury and trauma were reported to reduce TH levels [86] and also trigger viral reactivation (see Table 1). Therefore, TH is likely to participate in the regulation and maintenance of viral latency and reactivation. TH acts on almost every cell in the body including neurons. It is likely that TH contribute, at least in part, to the regulation of HSV-1 latency/reactivation.

c. Characterization of HSV-1 TKTRE

Early report revealed a pair of TRE located in the HSV-1 TK promoter and produced positive regulation [99]. Additional analyses indicated that these TK TREs are positioned between TATA box and the transcription initiation site arranged as "palindromes" with six nucleotides spacing each other (Figure 1). TREs in this format were also found in the promoters of TSHα and TSHβ, both exhibit negative regulations by TH in hypothalamic-pituitary-thyroid (HPT) axis [100]. It has been suggested that this TK TREs exhibited negative regulation by TH and TR in neuronal environment [51, 99].

Figure 1
figure 1

Characterization of HSV-1 TK TREs. Comparison of HSV-1 TK TREs to other palindrome TREs. These TREs were organized as inverted repeats with different numbers of nucleotides spacing in between them (see Consensus TREs). They are located after the TATA box and in front of the transcription initiation site (see TSHα TREs and TK TREs).

Full size image

i. TR negatively regulated HSV-1 TK transcription in neuronal cells

Analyses using mouse neuroblastoma cell lines N2a and N2aTRβ showed that HSV-1 TK promoter activity was repressed by liganded TR and activated in the presence of TR without TH using transient transfection assays [51]. It appears that TR exerted negative regulation on HSV-1 TK promoter in a neuronal cell line since the regulation was not observed in other cell lines such as 293HEK and Vero (data not shown). The binding of TR to negative TREs and the outcome of histone modification in neuronal cells were not well characterized. Chromatin immunoprecipitation (ChIP) assays showed that liganded TR exhibited strong interaction to the TK promoter via TREs. The binding was significantly reduced in the absence of TH [51]. Hypoacetylation was observation at the TK promoter by TH and TR using anti-acetyl H4 Ab [51]. These results indicated that liganded TR was recruited to the TK promoter and reduced the acetylation of histone tails at the TRE region.

ii. TK was repressed by TH and TR during viral infection

Based on the results of transfection assays, infections of cells with viruses were performed to investigate the TR/TH mediated regulation in neuronal cells. RT-PCR assays showed that TK transcription was inhibited by liganded TR at high moi while the viral protein synthesis was inhibited (unpublished data). It is noted that the TK promoter activity was efficiently repressed by TR/TH at low moi [51]. These results demonstrated that liganded TR repressed TK promoter activity in neuronal cells through chromatin modification via interaction with TK TREs.

iii. Liganded TR mediated TK inhibition can be reversed by TH removal

It was hypothesized that increasing TK expression may enhance HSV-1 replication/gene expression thus promoting viral DNA replication and α expression during reactivation [47]. Results from N2aTRβ cell culture model indicated that the removal of TH de-repressed the TK inhibition [51]. In addition, the same condition of TH washout can reactivate the expression of ICP0 [50], another important HSV-1 α gene for reactivation. Together these results further support the hypothesis that TH may have implication in the HSV-1 reactivation from latency through the induction of TK and ICP0.

6. In vitro TH-mediated HSV-1 latency cell culture model

A cell culture model was established to investigate the roles of TH/TR in the regulation of HSV-1 latency/reactivation [50, 51] (depicted in Figure 2). This system is based on the fact that over-expression of TR isoform β triggers N2a cells to differentiate in the presence of TH [101], mimicking the state of neurons where HSV-1 established latency. The plaque assays indicated that release of infectious virus was significantly decreased in the presence of TH with TR. Furthermore, TH washout de-repressed the virus replication and release [51]. These observations demonstrated the previous findings that TH availability played roles in the regulation of HSV-1 reactivation/latency.

Figure 2
figure 2

Establishment of a TH-regulated HSV-1 latency/reactivation cell culture model. Scheme of cell culture based HSV-1 latency/reactivation model.

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7. Conclusion and future direction

A number of studies suggested the possibilities that hormone imbalance may cause virus reactivation including HSV-1. The mouse neuroblastoma cell line N2a and N2aTRβ provided an efficient platform to investigate the molecular functions of TR and TH in the regulation of HSV-1 latency and reactivation. Current progress suggested that TR/TH inhibits the HSV-1 key gene expression, leading to blockade of viral replication and α expression therefore favors maintenance of latency in neurons. Transient or chronic hypothyroidism decreases the TH level and the lack of hormone relieves the inhibition of TK and ICP0 (likely to be indirect effect through TK activation [51] and insulator effects from the LAT regulatory region [50]), results in viral replication, gene expression, release of infectious viruses, and viral reactivation (Figure 3). Additional studies showed that this TR/TH-mediated regulation was due to, at least in part, by histone modification [50, 51]. In the future, the hypotheses should be tested in the animal models using TH and TR-selective thyromimetic agents. This will assist in explaining the roles of TH on the maintenance of viral latency, probably by blocking the α activation in latently-infected mice upon reactivation. Conversely, treatment with TH antagonists can be tested to see if they have effects on the expression of HSV-1 ICP0 and TK, viral replication, and viral reactivation. Standard established protocols such as hyperthermia will be used for reactivation and eye swabs will be taken at the appropriate times for analysis of reactivated infectious HSV-1. Trigeminal ganglia neurons from the treated infected mice will be removed for analyses of gene expression, chromatin remodeling, and measurement of HSV-1 copy number. In addition, removal of TH production by thyroidectomy can be used to confirm the regulatory effects during reactivation.

Figure 3
figure 3

Model of TR/TH-mediated HSV-1 latency and reactivation. The working hypothesis is that liganded TR repressed the transcription of TK in neurons, leading to inhibition of viral replication and α expression thus promoted the condition for latency. Transient or chronic hypothyroidism reduced the TH level and the shortage of hormone decreased the repression of TK and ICP0, therefore increased the viral replication, gene expression, and release of infectious viruses. All of these led to viral reactivation.

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Abbreviations

HSV:

Herpes simplex virus

TH:

Thyroid hormone

TR:

Thyroid hormone receptor

TK:

Thymidine kinase

TRE:

Thyroid hormone responsive elements

LAT:

Latency associate transcript

ICP0:

Infected cell protein 0

ChIP:

Chromatin immune-precipitation

IE:

Immediate early genes

References

  1. Kucharova S, Farkas R: Hormone nuclear receptors and their ligands: role in programmed cell death (review). Endocr Regul. 2002, 36 (1): 37-60.

    CAS  PubMed  Google Scholar 

  2. Fragu P: [The history of science with regard to the thyroid gland (1800-1960)]. Ann Endocrinol (Paris). 1999, 60 (1): 10-22.

    CAS  Google Scholar 

  3. Danzi S, Klein I: Potential uses of T3 in the treatment of human disease. Clin Cornerstone. 2005, 7 (Suppl 2): S9-15.

    Article  PubMed  Google Scholar 

  4. Jouravel N, Sablin E, Togashi M, Baxter JD, Webb P, Fletterick RJ: Molecular basis for dimer formation of TRbeta variant D355R. Proteins. 2009, 75 (1): 111-7. 10.1002/prot.22225

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Martinez L, Nascimento AS, Nunes FM, Phillips K, Aparicio R, Dias SM, Figueira AC, Lin JH, Nguyen P, Apriletti JW, Neves FA, Baxter JD, Webb P, Skaf MS, Polikarpov I: Gaining ligand selectivity in thyroid hormone receptors via entropy. Proc Natl Acad Sci USA. 2009, 106 (49): 20717-22. 10.1073/pnas.0911024106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Zheng J, Hashimoto A, Putnam M, Miller K, Koh JT: Development of a thyroid hormone receptor targeting conjugate. Bioconjug Chem. 2008, 19 (6): 1227-34. 10.1021/bc8000326

    Article  CAS  PubMed  Google Scholar 

  7. Machado DS, Sabet A, Santiago LA, Sidhaye AR, Chiamolera MI, Ortiga-Carvalho TM, Wondisford FE: A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo. Proc Natl Acad Sci USA. 2009, 106 (23): 9441-6. 10.1073/pnas.0903227106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. McEwan IJ, Nardulli AM: Nuclear hormone receptor architecture-form and dynamics: The 2009 FASEB Summer Conference on Dynamic Structure of the Nuclear Hormone Receptors. Nucl Recept Signal. 2009, 7: e011.

    PubMed Central  PubMed  Google Scholar 

  9. Teboul M, Guillaumond F, Grechez-Cassiau A, Delaunay F: The nuclear hormone receptor family round the clock. Mol Endocrinol. 2008, 22 (12): 2573-82. 10.1210/me.2007-0521

    Article  CAS  PubMed  Google Scholar 

  10. Lopes da Silva S, Burbach JP: The nuclear hormone-receptor family in the brain: classics and orphans. Trends Neurosci. 1995, 18 (12): 542-8. 10.1016/0166-2236(95)98376-A

    Article  CAS  PubMed  Google Scholar 

  11. Hiroi Y, Kim HH, Ying H, Furuya F, Huang Z, Simoncini T, Noma K, Ueki K, Nguyen NH, Scanlan TS, Moskowitz MA, Cheng SY, Liao JK: Rapid nongenomic actions of thyroid hormone. Proc Natl Acad Sci USA. 2006, 103 (38): 14104-9. 10.1073/pnas.0601600103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Chang C, Pan HJ: Thyroid hormone direct repeat 4 response element is a positive regulatory element for the human TR2 orphan receptor, a member of steroid receptor superfamily. Mol Cell Biochem. 1998, 189 (1-2): 195-200.

    Article  CAS  PubMed  Google Scholar 

  13. Velasco LF, Togashi M, Walfish PG, Pessanha RP, Moura FN, Barra GB, Nguyen P, Rebong R, Yuan C, Simeoni LA, Ribeiro RC, Baxter JD, Webb P, Neves FA: Thyroid hormone response element organization dictates the composition of active receptor. J Biol Chem. 2007, 282 (17): 12458-66. 10.1074/jbc.M610700200

    Article  CAS  PubMed  Google Scholar 

  14. Li B, Carey M, Workman JL: The role of chromatin during transcription. Cell. 2007, 128 (4): 707-19. 10.1016/j.cell.2007.01.015

    Article  CAS  PubMed  Google Scholar 

  15. Taylor TJ, Brockman MA, McNamee EE, Knipe DM: Herpes simplex virus. Front Biosci. 2002, 7: d752-64. 10.2741/taylor

    Article  CAS  PubMed  Google Scholar 

  16. Rozenberg F, Deback C, Agut H: Herpes Simplex Encephalitis: From Virus to Therapy. Infect Disord Drug Targets. 2011.

    Google Scholar 

  17. Lopez Garcia F, Enriquez Ascarza R, Rodriguez Martinez JC, Sirvent Pedreno AE: [Interferon therapy for herpes simplex virus infection in a 70 years old patient]. An Med Interna. 2002, 19 (11): 600-1.

    CAS  PubMed  Google Scholar 

  18. Everett RD: ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays. 2000, 22 (8): 761-70. 10.1002/1521-1878(200008)22:8<761::AID-BIES10>3.0.CO;2-A

    Article  CAS  PubMed  Google Scholar 

  19. Martinez PA, Diaz R, Gonzalez D, Oropesa L, Gonzalez R, Perez L, Viera J, Kouri V: The effect of highly active antiretroviral therapy on outcome of central nervous system herpesviruses infection in Cuban human immunodeficiency virus-infected individuals. J Neurovirol. 2007, 13 (5): 446-51. 10.1080/13550280701510088

    Article  CAS  PubMed  Google Scholar 

  20. Goel N, Mao H, Rong Q, Docherty JJ, Zimmerman D, Rosenthal KS: The ability of an HSV strain to initiate zosteriform spread correlates with its neuroinvasive disease potential. Arch Virol. 2002, 147 (4): 763-73. 10.1007/s007050200024

    Article  CAS  PubMed  Google Scholar 

  21. Shah A, Farooq AV, Tiwari V, Kim MJ, Shukla D: HSV-1 infection of human corneal epithelial cells: receptor-mediated entry and trends of re-infection. Mol Vis. 2010, 16: 2476-86.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Usatine RP, Tinitigan R: Nongenital herpes simplex virus. Am Fam Physician. 2010, 82 (9): 1075-82.

    PubMed  Google Scholar 

  23. Higaki S, Inoue Y, Yoshida A, Maeda N, Watanabe H, Shimomura Y: Case of bilateral multiple herpetic epithelial keratitis manifested as dendriform epithelial edema during primary Kaposi's varicelliform eruption. Jpn J Ophthalmol. 2008, 52 (2): 127-9. 10.1007/s10384-007-0514-6

    Article  PubMed  Google Scholar 

  24. Jonsson MK, Wahren B: Sexually transmitted herpes simplex viruses. Scand J Infect Dis. 2004, 36 (2): 93-101. 10.1080/00365540310018905

    Article  PubMed  Google Scholar 

  25. Brown JC: High G+C Content of Herpes Simplex Virus DNA: Proposed Role in Protection Against Retrotransposon Insertion. Open Biochem J. 2007, 1: 33-42. 10.2174/1874091X00701010033

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Borchers K, Goltz M, Ludwig H: Genome organization of the herpesviruses: minireview. Acta Vet Hung. 1994, 42 (2-3): 217-25.

    CAS  PubMed  Google Scholar 

  27. Weinheimer SP, McKnight SL: Transcriptional and post-transcriptional controls establish the cascade of herpes simplex virus protein synthesis. J Mol Biol. 1987, 195 (4): 819-33. 10.1016/0022-2836(87)90487-6

    Article  CAS  PubMed  Google Scholar 

  28. Burgos JS, Serrano-Saiz E, Sastre I, Valdivieso F: ICP47 mediates viral neuroinvasiveness by induction of TAP protein following intravenous inoculation of herpes simplex virus type 1 in mice. J Neurovirol. 2006, 12 (6): 420-7. 10.1080/13550280601009546

    Article  CAS  PubMed  Google Scholar 

  29. Beinert D, Neumann L, Uebel S, Tampe R: Structure of the viral TAP-inhibitor ICP47 induced by membrane association. Biochemistry. 1997, 36 (15): 4694-700. 10.1021/bi962940v

    Article  CAS  PubMed  Google Scholar 

  30. Cun W, Guo L, Zhang Y, Liu L, Wang L, Li J, Dong C, Wang J, Li Q: Transcriptional regulation of the Herpes Simplex Virus 1 alpha-gene by the viral immediate-early protein ICP22 in association with VP16. Sci China C Life Sci. 2009, 52 (4): 344-51. 10.1007/s11427-009-0051-2

    Article  CAS  PubMed  Google Scholar 

  31. LaBoissiere S, O'Hare P: Analysis of HCF, the cellular cofactor of VP16, in herpes simplex virus-infected cells. J Virol. 2000, 74 (1): 99-109. 10.1128/JVI.74.1.99-109.2000

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Gelman IH, Silverstein S: Identification of immediate early genes from herpes simplex virus that transactivate the virus thymidine kinase gene. Proc Natl Acad Sci USA. 1985, 82 (16): 5265-9. 10.1073/pnas.82.16.5265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Mark KE, Wald A, Magaret AS, Selke S, Olin L, Huang ML, Corey L: Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis. 2008, 198 (8): 1141-9. 10.1086/591913

    Article  PubMed Central  PubMed  Google Scholar 

  34. Antinone SE, Zaichick SV, Smith GA: Resolving the assembly state of herpes simplex virus during axon transport by live-cell imaging. J Virol. 2010, 84 (24): 13019-30. 10.1128/JVI.01296-10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Preston CM, Efstathiou S: Molecular basis of HSV latency and reactivation. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Chapter 33. Edited by: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K. 2007, Cambridge: Cambridge University Press, 2.

    Google Scholar 

  36. Chida Y, Mao X: Does psychosocial stress predict symptomatic herpes simplex virus recurrence? A meta-analytic investigation on prospective studies. Brain Behav Immun. 2009, 23 (7): 917-25. 10.1016/j.bbi.2009.04.009

    Article  PubMed  Google Scholar 

  37. Allen SJ, Hamrah P, Gate D, Mott KR, Mantopoulos D, Zheng L, Town T, Jones C, von Andrian UH, Freeman GJ, Sharpe AH, Benmohamed L, Ahmed R, Wechsler SL, Ghiasi H: The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1. J Virol. 2011, 85 (9): 4184-97. 10.1128/JVI.02290-10

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Perng GC, Jones C, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechsler SL: Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science. 2000, 287 (5457): 1500-3. 10.1126/science.287.5457.1500

    Article  CAS  PubMed  Google Scholar 

  39. Mador N, Goldenberg D, Cohen O, Panet A, Steiner I: Herpes simplex virus type 1 latency-associated transcripts suppress viral replication and reduce immediate-early gene mRNA levels in a neuronal cell line. J Virol. 1998, 72 (6): 5067-75.

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Perng GC, Slanina SM, Yukht A, Ghiasi H, Nesburn AB, Wechsler SL: The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits. J Virol. 2000, 74 (4): 1885-91. 10.1128/JVI.74.4.1885-1891.2000

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Giordani NV, Neumann DM, Kwiatkowski DL, Bhattacharjee PS, McAnany PK, Hill JM, Bloom DC: During herpes simplex virus type 1 infection of rabbits, the ability to express the latency-associated transcript increases latent-phase transcription of lytic genes. J Virol. 2008, 82 (12): 6056-60. 10.1128/JVI.02661-07

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Perng GC, Jones C: Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle. Interdiscip Perspect Infect Dis. 2010, 2010: 262415.

    PubMed Central  PubMed  Google Scholar 

  43. Amelio AL, McAnany PK, Bloom DC: A chromatin insulator-like element in the herpes simplex virus type 1 latency-associated transcript region binds CCCTC-binding factor and displays enhancer-blocking and silencing activities. J Virol. 2006, 80 (5): 2358-68. 10.1128/JVI.80.5.2358-2368.2006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Jacobson JG, Ruffner KL, Kosz-Vnenchak M, Hwang CB, Wobbe KK, Knipe DM, Coen DM: Herpes simplex virus thymidine kinase and specific stages of latency in murine trigeminal ganglia. J Virol. 1993, 67 (11): 6903-8.

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Kosz-Vnenchak M, Jacobson J, Coen DM, Knipe DM: Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons. J Virol. 1993, 67 (9): 5383-93.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Tal-Singer R, Lasner TM, Podrzucki W, Skokotas A, Leary JJ, Berger SL, Fraser NW: Gene expression during reactivation of herpes simplex virus type 1 from latency in the peripheral nervous system is different from that during lytic infection of tissue cultures. J Virol. 1997, 71 (7): 5268-76.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Nichol PF, Chang JY, Johnson EM, Olivo PD: Herpes simplex virus gene expression in neurons: viral DNA synthesis is a critical regulatory event in the branch point between the lytic and latent pathways. J Virol. 1996, 70 (8): 5476-86.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Lichtenstein MJ, Tilley WS, Sandler MP: The syndrome of hypothalamic hypopituitarism complicating viral meningoencephalitis. J Endocrinol Invest. 1982, 5 (2): 111-5.

    Article  CAS  PubMed  Google Scholar 

  49. Tang WW, Kaptein EM: Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. West J Med. 1989, 151 (6): 627-31.

    PubMed Central  CAS  PubMed  Google Scholar 

  50. Bedadala GR, Pinnoji RC, Palem JR, Hsia SC: Thyroid hormone controls the gene expression of HSV-1 LAT and ICP0 in neuronal cells. Cell Res. 2010, 20 (5): 587-98. 10.1038/cr.2010.50

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Hsia SC, Pinnoji RC, Bedadala GR, Hill JM, Palem JR: Regulation of herpes simplex virus type 1 thymidine kinase gene expression by thyroid hormone receptor in cultured neuronal cells. J Neurovirol. 2010, 16 (1): 13-24. 10.3109/13550280903552412

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Walter IB, Droz B: Nuclear and cytoplasmic triiodothyronine-binding sites in primary sensory neurons and Schwann cells: radioautographic study during development. J Neuroendocrinol. 1995, 7 (2): 127-36. 10.1111/j.1365-2826.1995.tb00675.x

    Article  CAS  PubMed  Google Scholar 

  53. Glauser L, Barakat Walter I: Differential distribution of thyroid hormone receptor isoform in rat dorsal root ganglia and sciatic nerve in vivo and in vitro. J Neuroendocrinol. 1997, 9 (3): 217-27.

    Article  CAS  PubMed  Google Scholar 

  54. Walter IB: Triiodothyronine exerts a trophic action on rat sensory neuron survival and neurite outgrowth through different pathways. Eur J Neurosci. 1996, 8 (3): 455-66. 10.1111/j.1460-9568.1996.tb01229.x

    Article  CAS  PubMed  Google Scholar 

  55. Barakat-Walter I, Riederer BM: Triiodothyronine and nerve growth factor are required to induce cytoplasmic dynein expression in rat dorsal root ganglion cultures. Brain Res Dev Brain Res. 1996, 96 (1-2): 109-19.

    Article  CAS  PubMed  Google Scholar 

  56. Marquart M, Bhattacharjee P, Zheng X, Kaufman H, Thompson H, Varnell E, Hill J: Ocular reactivation phenotype of HSV-1 strain F(MP)E, a corticosteroid-sensitive strain. Curr Eye Res. 2003, 26 (3-4): 205-9. 10.1076/ceyr.26.3.205.14890

    Article  PubMed  Google Scholar 

  57. Higaki S, Gebhardt BM, Lukiw WJ, Thompson HW, Hill JM: Effect of immunosuppression on gene expression in the HSV-1 latently infected mouse trigeminal ganglion. Invest Ophthalmol Vis Sci. 2002, 43 (6): 1862-9.

    PubMed  Google Scholar 

  58. Doherty MJ, Baxter AB, Longstreth WT: Herpes simplex virus encephalitis complicating myxedema coma treated with corticosteroids. Neurology. 2001, 56 (8): 1114-5.

    Article  CAS  PubMed  Google Scholar 

  59. Padgett DA, Sheridan JF, Dorne J, Berntson GG, Candelora J, Glaser R: Social stress and the reactivation of latent herpes simplex virus type 1. Proc Natl Acad Sci USA. 1998, 95 (12): 7231-5. 10.1073/pnas.95.12.7231

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Glaser R, Friedman SB, Smyth J, Ader R, Bijur P, Brunell P, Cohen N, Krilov LR, Lifrak ST, Stone A, Toffler P: The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point. Brain Behav Immun. 1999, 13 (3): 240-51. 10.1006/brbi.1999.0566

    Article  CAS  PubMed  Google Scholar 

  61. Jenkins FJ, Baum A: Stress and reactivation of latent herpes simplex virus: a fusion of behavioral medicine and molecular biology. Ann Behav Med. 1995, 17 (2): 116-23. 10.1007/BF02895060

    Article  CAS  PubMed  Google Scholar 

  62. Blondeau JM, Aoki FY, Glavin GB: Stress-induced reactivation of latent herpes simplex virus infection in rat lumbar dorsal root ganglia. J Psychosom Res. 1993, 37 (8): 843-9. 10.1016/0022-3999(93)90173-D

    Article  CAS  PubMed  Google Scholar 

  63. Buske-Kirschbaum A, Geiben A, Wermke C, Pirke KM, Hellhammer D: Preliminary evidence for Herpes labialis recurrence following experimentally induced disgust. Psychother Psychosom. 2001, 70 (2): 86-91. 10.1159/000056231

    Article  CAS  PubMed  Google Scholar 

  64. Friedman Y, Bacchus R, Raymond R, Joffe RT, Nobrega JN: Acute stress increases thyroid hormone levels in rat brain. Biol Psychiatry. 1999, 45 (2): 234-7. 10.1016/S0006-3223(98)00054-7

    Article  CAS  PubMed  Google Scholar 

  65. Turakulov I, Burikhanov RB, Patkhitdinov PP, Myslitskaia AI: [Effect of immobilization stress on the level of thyroid hormone secretion]. Probl Endokrinol (Mosk). 1993, 39 (5): 47-8.

    CAS  Google Scholar 

  66. Stein EJ, da Silveira Filho NG, Machado DC, Hipolide DC, Barlow K, Nobrega JN: Chronic mild stress induces widespread decreases in thyroid hormone alpha1 receptor mRNA levels in brain--reversal by imipramine. Psychoneuroendocrinology. 2009, 34 (2): 281-6. 10.1016/j.psyneuen.2008.09.005

    Article  CAS  PubMed  Google Scholar 

  67. Engstrom WW, Markardt B: The effects of serious illness and surgical stress on the circulating thyroid hormone. J Clin Endocrinol Metab. 1955, 15 (8): 953-63. 10.1210/jcem-15-8-953

    Article  CAS  PubMed  Google Scholar 

  68. May JD, Deaton JW, Reece FN, Branton SL: Effect of acclimation and heat stress on thyroid hormone concentration. Poult Sci. 1986, 65 (6): 1211-3.

    Article  CAS  PubMed  Google Scholar 

  69. Portolani M, Cermelli C, Moroni A, Bertolani MF, Di Luca D, Cassai E, Sabbatini AM: Human herpesvirus-6 infections in infants admitted to hospital. J Med Virol. 1993, 39 (2): 146-51. 10.1002/jmv.1890390211

    Article  CAS  PubMed  Google Scholar 

  70. Colgin MA, Smith RL, Wilcox CL: Inducible cyclic AMP early repressor produces reactivation of latent herpes simplex virus type 1 in neurons in vitro. J Virol. 2001, 75 (6): 2912-20. 10.1128/JVI.75.6.2912-2920.2001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. van Kraaij MG, Verdonck LF, Rozenberg-Arska M, Dekker AW: Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence. Bone Marrow Transplant. 2002, 30 (5): 303-9. 10.1038/sj.bmt.1703643

    Article  CAS  PubMed  Google Scholar 

  72. Sawtell NM, Thompson RL: Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. J Virol. 1992, 66 (4): 2150-6.

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Mustafa S, Al-Bader MD, Elgazzar AH, Alshammeri J, Gopinath S, Essam H: Effect of hyperthermia on the function of thyroid gland. Eur J Appl Physiol. 2008, 103 (3): 285-8. 10.1007/s00421-008-0701-2

    Article  CAS  PubMed  Google Scholar 

  74. Brzezinska-Slebodzinska E: Fever induced oxidative stress: the effect on thyroid status and the 5'-monodeiodinase activity, protective role of selenium and vitamin E. J Physiol Pharmacol. 2001, 52 (2): 275-84.

    CAS  PubMed  Google Scholar 

  75. Ljunggren JG, Kallner G, Tryselius M: The effect of body temperature on thyroid hormone levels in patients with non-thyroidal illness. Acta Med Scand. 1977, 202 (6): 459-62.

    CAS  PubMed  Google Scholar 

  76. Shafer RB, Oken MM, Elson MK: Effects of fever and hyperthermia on thyroid function. J Nucl Med. 1980, 21 (12): 1158-61.

    CAS  PubMed  Google Scholar 

  77. Psychological stress and other potential triggers for recurrences of herpes simplex virus eye infections. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000, 118 (12): 1617-25.

  78. Beyer CF, Hill JM, Reidy JJ, Beuerman RW: Corneal nerve disruption reactivates virus in rabbits latently infected with HSV-1. Invest Ophthalmol Vis Sci. 1990, 31 (5): 925-32.

    CAS  PubMed  Google Scholar 

  79. Khan SA, Wingard JR: Infection and mucosal injury in cancer treatment. J Natl Cancer Inst Monogr. 2001, 31-6. 29.

  80. Jiang YH, Tian KB, Liu WD, Fan TH, Li F: [Thyroid hormone level change in patients undergoing oral and maxillofacial surgery]. Shanghai Kou Qiang Yi Xue. 2007, 16 (6): 611-3.

    CAS  PubMed  Google Scholar 

  81. Marques-Silva L, Castro WH, Gomez EL, Guimaraes AL, Silva MS, Gomez RS: The impact of dental surgery on HSV-1 reactivation in the oral mucosa of seropositive patients. J Oral Maxillofac Surg. 2007, 65 (11): 2269-72. 10.1016/j.joms.2007.05.029

    Article  PubMed  Google Scholar 

  82. Hyland PL, Coulter WA, Abu-Ruman I, Fulton CR, O'Neill HJ, Coyle PV, Lamey PJ: Asymptomatic shedding of HSV-1 in patients undergoing oral surgical procedures and attending for noninvasive treatment. Oral Dis. 2007, 13 (4): 414-8. 10.1111/j.1601-0825.2007.01316.x

    Article  CAS  PubMed  Google Scholar 

  83. Hedner E, Vahlne A, Bergstrom T, Hirsch JM: Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues. J Oral Pathol Med. 1993, 22 (5): 214-20. 10.1111/j.1600-0714.1993.tb01059.x

    Article  CAS  PubMed  Google Scholar 

  84. Haviland MG, Sonne JL, Anderson DL, Nelson JC, Sheridan-Matney C, Nichols JG, Carlton EI, Murdoch WG: Thyroid hormone levels and psychological symptoms in sexually abused adolescent girls. Child Abuse Negl. 2006, 30 (6): 589-98. 10.1016/j.chiabu.2005.11.011

    Article  PubMed  Google Scholar 

  85. Arem R, Wiener GJ, Kaplan SG, Kim HS, Reichlin S, Kaplan MM: Reduced tissue thyroid hormone levels in fatal illness. Metabolism. 1993, 42 (9): 1102-8. 10.1016/0026-0495(93)90266-Q

    Article  CAS  PubMed  Google Scholar 

  86. Woolf PD, Lee LA, Hamill RW, McDonald JV: Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation. Am J Med. 1988, 84 (2): 201-8. 10.1016/0002-9343(88)90414-7

    Article  CAS  PubMed  Google Scholar 

  87. Franco-Vidal V, Nguyen DQ, Guerin J, Darrouzet V: Delayed facial paralysis after vestibular schwannoma surgery: role of herpes viruses reactivation--our experience in eight cases. Otol Neurotol. 2004, 25 (5): 805-10. 10.1097/00129492-200409000-00026

    Article  PubMed  Google Scholar 

  88. Molloy S, Allcutt D, Brennan P, Farrell MA, Perryman R, Brett FM: Herpes simplex encephalitis occurring after chemotherapy, surgery, and stereotactic radiotherapy for medulloblastoma. Arch Pathol Lab Med. 2000, 124 (12): 1809-12.

    CAS  PubMed  Google Scholar 

  89. Bourgeois M, Vinikoff L, Lellouch-Tubiana A, Sainte-Rose C: Reactivation of herpes virus after surgery for epilepsy in a pediatric patient with mesial temporal sclerosis: case report. Neurosurgery. 1999, 44 (3): 633-5. discussion 635-6.

    Article  CAS  PubMed  Google Scholar 

  90. Tenser RB, Edris WA, Hay KA: Herpes simplex virus latent infection: reactivation and elimination of latency after neurectomy. Virology. 1988, 167 (1): 302-5. 10.1016/0042-6822(88)90085-2

    Article  CAS  PubMed  Google Scholar 

  91. Porteous C, Bradley JA, Hamilton DN, Ledingham IM, Clements GB, Robinson CG: Herpes simplex virus reactivation in surgical patients. Crit Care Med. 1984, 12 (8): 626-8. 10.1097/00003246-198408000-00003

    Article  CAS  PubMed  Google Scholar 

  92. Hartel W, Petermann C, Petermann U, Fischer M: [Thyroid hormone levels after surgical stress reaction (author's transl)]. MMW Munch Med Wochenschr. 1980, 122 (43): 1505-7.

    CAS  PubMed  Google Scholar 

  93. Dagan O, Vidne B, Josefsberg Z, Phillip M, Strich D, Erez E: Relationship between changes in thyroid hormone level and severity of the postoperative course in neonates undergoing open-heart surgery. Paediatr Anaesth. 2006, 16 (5): 538-42. 10.1111/j.1460-9592.2005.01808.x

    Article  PubMed  Google Scholar 

  94. Nicolatou-Galitis O, Dardoufas K, Markoulatos P, Sotiropoulou-Lontou A, Kyprianou K, Kolitsi G, Pissakas G, Skarleas C, Kouloulias V, Papanicolaou V, Legakis NJ, Velegraki A: Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. J Oral Pathol Med. 2001, 30 (8): 471-80. 10.1034/j.1600-0714.2001.030008471.x

    Article  CAS  PubMed  Google Scholar 

  95. Silvano G, Lazzari G, Resta F, Buccoliero G, Pezzella G, Pisconti S: A Herpes simplex virus-1 fatal encephalitis following chemo-radiotherapy, steroids and prophylactic cranial irradiation in a small cell lung cancer patient. Lung Cancer. 2007, 57 (2): 243-6. 10.1016/j.lungcan.2007.01.031

    Article  CAS  PubMed  Google Scholar 

  96. Airoldi M, Gabriele P, Brossa PC, Pedani F, Tseroni V, D'Alberto M, Ragona R: Serum thyroid hormone changes in head and neck cancer patients treated with microwave hyperthermia on lymph node metastasis. Cancer. 1990, 65 (4): 901-7. 10.1002/1097-0142(19900215)65:4<901::AID-CNCR2820650414>3.0.CO;2-M

    Article  CAS  PubMed  Google Scholar 

  97. Pirnat E, Zaletel K, Gaberscek S, Fidler V, Hojker S: Early changes of thyroid hormone concentrations after (131)I therapy in Graves' patients pretreated or not with methimazole. Nuklearmedizin. 2004, 43 (4): 129-34.

    CAS  PubMed  Google Scholar 

  98. Nakajo M, Tsuchimochi S, Tanabe H, Nakabeppu Y, Jinguji M: Three basic patterns of changes in serum thyroid hormone levels in Graves' disease during the one-year period after radioiodine therapy. Ann Nucl Med. 2005, 19 (4): 297-308. 10.1007/BF02984622

    Article  CAS  PubMed  Google Scholar 

  99. Park HY, Davidson D, Raaka BM, Samuels HH: The herpes simplex virus thymidine kinase gene promoter contains a novel thyroid hormone response element. Mol Endocrinol. 1993, 7 (3): 319-30. 10.1210/me.7.3.319

    CAS  PubMed  Google Scholar 

  100. Chatterjee VK, Lee JK, Rentoumis A, Jameson JL: Negative regulation of the thyroid-stimulating hormone alpha gene by thyroid hormone: receptor interaction adjacent to the TATA box. Proc Natl Acad Sci USA. 1989, 86 (23): 9114-8. 10.1073/pnas.86.23.9114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Lebel JM, Dussault JH, Puymirat J: Overexpression of the beta 1 thyroid receptor induces differentiation in neuro-2a cells. Proc Natl Acad Sci USA. 1994, 91 (7): 2644-8. 10.1073/pnas.91.7.2644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgements

Support of the National Institutes of Health and the National Center for Research Resources Grant P20RR016456 is gratefully acknowledged.

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  1. Department of Pharmaceutical Sciences, University of Maryland, Eastern Shore School of Pharmacy, Princess Anne, Maryland, 21853, USA

    Shao-Chung Hsia, Gautam R Bedadala & Matthew D Balish

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  1. Shao-Chung Hsia
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Hsia, SC., Bedadala, G.R. & Balish, M.D. Effects of thyroid hormone on HSV-1 gene regulation: implications in the control of viral latency and reactivation. Cell Biosci 1, 24 (2011). https://doi.org/10.1186/2045-3701-1-24

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Keywords

  • Thyroid Hormone
  • Thymidine Kinase
  • Trigeminal Ganglion
  • Latency Associate Transcript
  • Herpes Simplex Virus

Cell & Bioscience

ISSN: 2045-3701

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