Proximity to PML Nuclear Bodies Regulates HIV-1 Latency in CD4+ T Cells

Lušić, Marina; Marini, Bruna; Ali, Hashim; Lucic, Bojana; Luzzati, Roberto; Giacca, Mauro

doi:10.1016/j.chom.2013.05.006

Cited by 97 publications

(117 citation statements)

References 57 publications

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“…Under this model, inflammatory stimuli increase the activity of the transcriptional activators NF-κB and NFAT, which are required for the transcription of viral genes (109, 110) and p53, which coincidently mediates apoptosis (111). Antioxidants may therefore silence transcriptional activity (109,110), while pro-oxidants, such as arsenic trioxide, may reactivate the viral reservoir (112). By the same token, both NO donors and endogenously generated NO may stimulate HIV reactivation (113).…”

Section: Treating Hiv/aids By Increasing Oxidative Stress: Results Frmentioning

confidence: 99%

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Benhar¹,

Shytaj²,

Stamler³

et al. 2016

Journal of Clinical Investigation

144

115

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Section: Treating Hiv/aids By Increasing Oxidative Stress: Results Frmentioning

confidence: 99%

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Benhar¹,

Shytaj²,

Stamler³

et al. 2016

Journal of Clinical Investigation

144

115

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“…Nevertheless, both studies indicate an unconventional mobility of PML-NBs, which appear to sense viral nucleoprotein complexes or replication intermediates, resulting in movement of the respective proteins even to the cytoplasm. Additionally, PML and hDaxx were implicated as contributing to the control of retroviral latency via epigenetic repression (12,13).…”

Section: Pml-nbs and Intrinsic Immunitymentioning

confidence: 99%

Emerging Role of PML Nuclear Bodies in Innate Immune Signaling

Scherer

Stamminger

2016

J Virol

150

168

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Research in the last 2 decades has demonstrated that a specific organelle of the cell nucleus, termed PML nuclear body (PML-NB) or nuclear domain 10 (ND10), is frequently modified during viral infection. This correlates with antagonization of a direct repressive function of individual PML-NB components, such as the PML, hDaxx, Sp100, or ATRX protein, that are able to act as cellular restriction factors. Recent studies now reveal an emerging role of PML-NBs as coregulatory structures of both type I and type II interferon responses. This emphasizes that targeting of PML-NBs by viral regulatory proteins has evolved as a strategy to compromise intrinsic antiviral defense and innate immune responses. P romyelocytic leukemia (PML) protein, a member of the tripartite motif (TRIM) protein family, is the key component of subnuclear structures known as PML nuclear bodies (PML-NBs) or nuclear domains 10 (ND10). PML-NBs are dynamic foci that consist of numerous permanently or transiently associated proteins and, consequently, have been implicated in the regulation of diverse cellular functions, including the cell cycle, apoptosis, senescence, stress, and DNA damage responses (reviewed in reference 1). Although the underlying biochemical function of these subnuclear structures is still unclear, three models can be found in the literature, proposing PML-NBs to be nuclear protein depots, sites of nuclear activities (e.g., transcription), or hotspots for posttranslational modifications. In particular, since nearly all PMLassociated proteins are modified by SUMO and SUMOylation of PML is essential for the integrity of PML-NBs, these structures may form "catalytic surfaces" for SUMOylation (1). This is of importance since recent studies suggest that the SUMO pathway is required for the regulation of innate immune signaling and intrinsic immunity during viral infection (reviewed in reference 2). The observation that PML-NBs are targeted and modified by many viruses during infection set off a longstanding debate as to whether PML-NBs exert a pro-or antiviral function and led to a fruitful area of virology research over the past 20 years. Interestingly, these studies revealed that viruses, even representatives of the same virus family, trigger diverse modifications of PML-NBs during infection, ranging from proteasomal degradation of NB components by herpes simplex virus type 1 (HSV-1), to dispersal of PML-NBs by human cytomegalovirus (HCMV), to a rearrangement of PML-NB foci into nuclear track-like structures by adenoviruses or a relocalization of PML into cytoplasmic bodies by HIV-1 (3-5). While there are a few examples of viral factors that undergo interactions with PML-NBs in order to exploit these structures for the benefit of the virus, the main body of evidence supports a role of PML-NBs as components of the antiviral defense against a variety of DNA and RNA viruses (reviewed in reference 3). PML-NBs AND INTRINSIC IMMUNITYThe role of PML-NBs in intrinsic immunity, which represents the first line of intracellular defense agains...

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“…Chromatin immunoprecipitation was performed as described, 31 with modification detailed in the Methods in the Online Data Supplement. The primers used are listed in Online Table III.…”

Section: Chromatin Immunoprecipitationmentioning

confidence: 99%

Epigenetic Modification at Notch Responsive Promoters Blunts Efficacy of Inducing Notch Pathway Reactivation After Myocardial Infarction

Felician

Collesi

Lušić

et al. 2014

Circulation Research

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Rationale:The Notch pathway plays a key role in stimulating mammalian cardiomyocyte proliferation during development and in the early postnatal life; in adult zebrafish, reactivation of this pathway is also essential to drive cardiac regeneration after injury.Objective: We wanted to assess efficacy of Notch pathway stimulation in neonatal and adult hearts as a means to induce cardiac regeneration after myocardial infarction in mice. Methods and Results:

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Proximity to PML Nuclear Bodies Regulates HIV-1 Latency in CD4+ T Cells

Cited by 97 publications

References 57 publications

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Emerging Role of PML Nuclear Bodies in Innate Immune Signaling

Epigenetic Modification at Notch Responsive Promoters Blunts Efficacy of Inducing Notch Pathway Reactivation After Myocardial Infarction

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