The Herpes Simplex Virus Type 2 R1 Protein Kinase (ICP10 PK) Functions as a Dominant Regulator of Apoptosis in Hippocampal Neurons Involving Activation of the ERK Survival Pathway and Upregulation of the Antiapoptotic Protein Bag-1

Perkins, Darren J.; Pereira, Edna F. R.; Aurelian, Laure

doi:10.1128/jvi.77.2.1292-1305.2003

Cited by 89 publications

(148 citation statements)

References 91 publications

(195 reference statements)

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“…Similar results are also seen in murine bone marrow-derived DC. Although apoptosis is well-documented as a global cellular response to viral infection (including HSV), these results are somewhat surprising as both HSV-1 and -2 encode several gene products that effectively interfere with this pathway [68][69][70][71][72][73][74]. Nevertheless HSV-1 also induces apoptosis in monocytes and T cells [75][76][77].…”

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confidence: 99%

Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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confidence: 99%

Langerhans cells and viral immunity

2008

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“…Además del incremento en la expresión de la proteína Mcl-1, se encontró que la activación de la vía de ERK inducía la sobre-expresión de otra proteína anti-apoptótica denominada Bag-1 43 . De forma interesante, se ha encontrado que la sobre-expresión de Bag-1 también es inducida como un mecanismo antiapoptótico en otros patógenos como el VHS tipo 2 y la bacteria Clamidia trachomatis 44,45 .…”

Section: • Incremento En La Expresión De Proteínas Celularesunclassified

Modulación de la apoptosis por cytomegalovirus en la perspectiva del sistema nervioso central

González-Sánchez¹,

Silva‐Ramírez²,

Campo³

2016

Rev. chil. infectol.

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“…Previous studies had shown that ICP10PK overrides caspase-dependent cascades, [11][12][13][14][15][16][17] but its ability to inhibit caspase-independent death programs is still unknown. In a first series of experiments to address this question, neuronally differentiated PC12, PC139 and PC47 cells were treated with MPP+, exposed to the mitochondrionselective dye MitoTracker Red 580 and stained with Alexa Fluor 488-labeled AIF antibody, as described in 'Materials and methods'.…”

Section: Icp10pk Inhibits Mpp+-triggered Aif Release/nuclear Translocmentioning

confidence: 99%

“…To examine whether ICP10PK inhibits MPP+-induced cell death, neuronally differentiated PC12 cells were treated with the ICP10PK vector DRR, that is neuroprotective in other toxicity paradigms, 11,[13][14][15][16][17] and exposed to MPP+ (1 mM, 24 h) at 24 h after infection. PCD was evaluated based on DNA fragmentation measured by terminal transferase dUTP nick-end labeling (TUNEL).…”

Section: Icp10pk Inhibits Mpp+-induced Toxicitymentioning

confidence: 99%

“…Neuroprotection was seen in cultured cells, organotypic slices and animal models, and it was through the activation of redundant survival pathways. [11][12][13][14][15][16] Most importantly, the surviving neurons retained synaptic function, 11,13,14 suggesting that ICP10PK has strong and versatile neuroprotective potential that might be harnessed in the treatment of PD. However, the ability of ICP10PK to inhibit caspaseindependent PCD is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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ICP10PK inhibits calpain-dependent release of apoptosis-inducing factor and programmed cell death in response to the toxin MPP+

et al. 2008

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Apoptosis is a widely accepted component of the pathogenesis of Parkinson's disease (PD), a debilitating neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. However, additional death programs were implicated, and current understanding of the cycle of intracellular events that leads to the demise of these neurons is limited. Gene therapy strategies were proposed to inhibit apoptosis, but they have met with relatively limited success. Here we report that the antiapoptotic herpes simplex virus type 2 gene ICP10PK protects neuronally differentiated PC12 cells from death caused by 1-methyl-4-phenylpyridinium (in vitro PD model) through inhibition of calpain I activation and the resulting inhibition of Bax translocation to the mitochondria, apoptosis-inducing factor release and caspase-3 activation. Neuroprotection is through ICP10PK-mediated activation of the PI3-K/Akt survival pathway and upregulation/stabilization of the antiapoptotic protein Bcl-2 and the cytoprotective chaperone heat-shock protein 70.

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The Herpes Simplex Virus Type 2 R1 Protein Kinase (ICP10 PK) Functions as a Dominant Regulator of Apoptosis in Hippocampal Neurons Involving Activation of the ERK Survival Pathway and Upregulation of the Antiapoptotic Protein Bag-1

Cited by 89 publications

References 91 publications

Langerhans cells and viral immunity

Langerhans cells and viral immunity

Modulación de la apoptosis por cytomegalovirus en la perspectiva del sistema nervioso central

ICP10PK inhibits calpain-dependent release of apoptosis-inducing factor and programmed cell death in response to the toxin MPP+

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