Viral genome silencing by neuronal sirtuin 1

Picchione, Kelly E.; Bhattacharjee, Abhishek

doi:10.1007/s13365-010-0012-3

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…Silencing RNA (siRNA) knockdown of all seven human sirtuins (SIRT1–7) has been shown to increase AdV-C5 titers by 1.5- to 3-fold [88]. In the same vein, activation of sirtuins through resveratrol treatment inhibits adenovirus DNA replication [89, 90]. Another NAD + -dependent enzyme to have been studied in lytic infection is Poly (ADP-Ribose) Polymerase 1 (PARP1); the AdV E4orf4 protein has been found to increase production of viral progeny through inhibition of PARP1, which is activated by the infection-induced DNA damage response (DDR) [91].…”

Section: Discussionmentioning

confidence: 99%

NAD-linked mechanisms of gene de-repression and a novel role for CtBP in persistent adenovirus infection of lymphocytes

Dickherber

Garnett-Benson

2019

Virol J

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BackgroundAdenovirus (AdV) infection is ubiquitous in the human population and causes acute infection in the respiratory and gastrointestinal tracts. In addition to lytic infections in epithelial cells, AdV can persist in a latent form in mucosal lymphocytes, and nearly 80% of children contain viral DNA in the lymphocytes of their tonsils and adenoids. Reactivation of latent AdV is thought to be the source of deadly viremia in pediatric transplant patients. Adenovirus latency and reactivation in lymphocytes is not well studied, though immune cell activation has been reported to promote productive infection from latency. Lymphocyte activation induces global changes in cellular gene expression along with robust changes in metabolic state. The ratio of free cytosolic NAD+/NADH can impact gene expression via modulation of transcriptional repressor complexes. The NAD-dependent transcriptional co-repressor C-terminal Binding Protein (CtBP) was discovered 25 years ago due to its high affinity binding to AdV E1A proteins, however, the role of this interaction in the viral life cycle remains unclear.MethodsThe dynamics of persistently- and lytically-infected cells are evaluated. RT-qPCR is used to evaluate AdV gene expression following lymphocyte activation, treatment with nicotinamide, or disruption of CtBP-E1A binding.ResultsPMA and ionomycin stimulation shifts the NAD+/NADH ratio in lymphocytic cell lines and upregulates viral gene expression. Direct modulation of NAD+/NADH by nicotinamide treatment also upregulates early and late viral transcripts in persistently-infected cells. We found differential expression of the NAD-dependent CtBP protein homologs between lymphocytes and epithelial cells, and inhibition of CtBP complexes upregulates AdV E1A expression in T lymphocyte cell lines but not in lytically-infected epithelial cells.ConclusionsOur data provide novel insight into factors that can regulate AdV infections in activated human lymphocytes and reveal that modulation of cellular NAD+/NADH can de-repress adenovirus gene expression in persistently-infected lymphocytes. In contrast, disrupting the NAD-dependent CtBP repressor complex interaction with PxDLS-containing binding partners paradoxically alters AdV gene expression. Our findings also indicate that CtBP activities on viral gene expression may be distinct from those occurring upon metabolic alterations in cellular NAD+/NADH ratios or those occurring after lymphocyte activation.

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Section: Discussionmentioning

confidence: 99%

NAD-linked mechanisms of gene de-repression and a novel role for CtBP in persistent adenovirus infection of lymphocytes

Dickherber

Garnett-Benson

2019

Virol J

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“…Starting from the reports available in literature in which SIRT1 and its positive modulation by resveratrol inhibit varicella zoster virus replication, [24], human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) [25] transactivation, and viral transgene expression of adenovirus in neuronal cells [26], Shenk et al [27] patented the effects of the known sirtuin inhibitors EX-527, cambinol, tenovin-6, salermide, and of the SIRT1 activators resveratrol and the pyrroloquinoxaline CAY10602 ( Figure 1) in virus production. First, the authors demonstrated that the prominent positive effect on human cytomegalovirus (HCMV) replication in infected MRC5 fibroblasts was mainly observed when mitochondrial SIRT3--5 were inhibited by short interfering RNA (siRNA), thus indicating for the first time that the activation of those isoforms could be useful targets for antiviral therapy.…”

Section: Sirtuin Inhibitorsmentioning

confidence: 99%

Sirtuin modulators: an updated patent review (2012 – 2014)

Mellini

Valente

Mai

2014

Expert Opinion on Therapeutic Patents

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The effective role of sirtuins in cancer is still controversial, because some of them seem to have tumor-promoter as well as tumor-suppressor properties. Thus, few patents describing SIRT inhibitors have been found in 2012 - 2014 period. Despite the still active debate on their role as direct or indirect activators of SIRT1, sirtuin-activating compounds are actually subjected to intense research for the ability to treat neurodegenerative diseases, metabolic disorders, inflammation, vascular system injuries, wound healing and endothelial dysfunctions. A great number of clinical trials are reported with either SIRT inhibitors or activators, thus it is possible that in the foreseeable future one or more of them will enter in the clinical arena.

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“…However, SIRT1 has been implicated in the progression of human immunodeficiency virus 1 (HIV-1) [102,107,108,109], human papillomavirus (HPV) [110] and vesicular stomatitis virus (VSV) [111] infection. SIRT1 has also been proposed to control the reactivation of latent varicella zoster virus (VZV) in neurons through the reduction of intracellular NAD + levels [112]. Additionally, canine coronavirus (CCoV-II) infection has been shown to induce the expression of SIRT1, SIRT3 and SIRT4 [113], suggesting that the regulation of individual sirtuins is virus specific.…”

Section: Host Employment Of Hdacs and Acetylation In Defense Againmentioning

confidence: 99%

Histone Deacetylases in Herpesvirus Replication and Virus-Stimulated Host Defense

Guise

Budayeva

Diner

et al. 2013

Viruses

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Emerging evidence highlights a critical role for protein acetylation during herpesvirus infection. As prominent modulators of protein acetylation, histone deacetylases (HDACs) are essential transcriptional and epigenetic regulators. Not surprisingly, viruses have evolved a wide array of mechanisms to subvert HDAC functions. Here, we review the mechanisms underlying HDAC regulation during herpesvirus infection. We next discuss the roles of acetylation in host defense against herpesvirus infection. Finally, we provide a perspective on the contribution of current mass spectrometry-based “omic” technologies to infectious disease research, offering a systems biology view of infection.

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Viral genome silencing by neuronal sirtuin 1

Cited by 5 publications

References 20 publications

NAD-linked mechanisms of gene de-repression and a novel role for CtBP in persistent adenovirus infection of lymphocytes

NAD-linked mechanisms of gene de-repression and a novel role for CtBP in persistent adenovirus infection of lymphocytes

Sirtuin modulators: an updated patent review (2012 – 2014)

Histone Deacetylases in Herpesvirus Replication and Virus-Stimulated Host Defense

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