RESUMEN
Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly implicated in MCC pathogenesis. Currently, little is known regarding the virus-host cell interactions which support virus replication and virus-induced mechanisms in cellular transformation and metastasis. Here we identify a new function of MCPyV small T antigen (ST) as an inhibitor of NF-κB-mediated transcription. This effect is due to an interaction between MCPyV ST and the NF-κB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits IκB kinase α (IKKα)/IKKß-mediated IκB phosphorylation, which limits translocation of the NF-κB heterodimer to the nucleus. Regulation of this process involves a previously undescribed interaction between MCPyV ST and the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein phosphatase 2A (PP2A) Aß, but not PP2A Aα. Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell.
Asunto(s)
Antígenos Virales de Tumores/metabolismo , Carcinoma de Células de Merkel/metabolismo , Quinasa I-kappa B/metabolismo , Poliomavirus de Células de Merkel/metabolismo , Infecciones por Polyomavirus/metabolismo , Infecciones Tumorales por Virus/metabolismo , Antígenos Virales de Tumores/genética , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/inmunología , Carcinoma de Células de Merkel/virología , Línea Celular , Humanos , Quinasa I-kappa B/genética , Quinasa I-kappa B/inmunología , Inmunidad Innata , Poliomavirus de Células de Merkel/genética , FN-kappa B/genética , FN-kappa B/inmunología , Fosforilación , Infecciones por Polyomavirus/genética , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Unión Proteica , Infecciones Tumorales por Virus/genética , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virologíaRESUMEN
The optimal treatment for type II endoleaks remains unclear. The present report describes a case of ischemic skin ulceration after glue embolization of a type II endoleak with challenging access in a multiply comorbid 82-year-old woman with an expanding aneurysm sac 3 years after endovascular aneurysm repair. Embolization was performed from a proximal position with an n-butyl cyanoacrylate/Ethiodol mixture to allow flow into the endoleak because direct sac puncture was hazardous. One week after intervention, an eschar, which progressed to superficial necrosis as a result of partial nontarget delivery of sclerosant, developed over the left iliac crest. The eschar was self-limiting, with complete resolution by 6 months.