Glycoprotein C (gC), one of ∼12 HSV-1 envelope glycoproteins, carries out several important functions during infection, including the enhancement of virion attachment by binding to host cell heparan sulfate proteoglycans (HSPG). Here we report that gC can also enhance the release of cell-free progeny virions at the end of the infectious cycle. This activity was observed in multiple cellular contexts including Vero cells and immortalized human keratinocytes.
View Article and Find Full Text PDFBackgroundMerkel cell carcinoma (MCC) is an aggressive neuroendocrine (NE) skin cancer caused by severe UV-induced mutations or expression of Merkel cell polyomavirus (MCPyV) large and small T antigens (LT and ST). Despite deep genetic differences between MCPyV-positive and -negative subtypes, current clinical diagnostic markers are indistinguishable, and the expression profile of MCC tumors is, to our knowledge, unexplored.MethodsHere, we leveraged bulk and single-cell RNA-Seq of patient-derived tumor biopsies and cell lines to explore the underlying transcriptional environment of MCC.
View Article and Find Full Text PDFMerkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with 2 etiologies. Merkel cell polyomavirus (MCPyV) integration is present in about 80% of all MCC. Virus-positive MCC (MCCP) tumors have few somatic mutations and usually express WT p53 (TP53).
View Article and Find Full Text PDFMerkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine (NE) features, limited treatment options, and a lack of druggable targets. There is no reported involvement of the MUC1-C oncogenic protein in MCC progression. We show here that MUC1-C is broadly expressed in MCCs and at higher levels in Merkel cell polyomavirus (MCPyV)-positive (MCCP) relative to MCPyV-negative (MCCN) tumors.
View Article and Find Full Text PDFPolyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized.
View Article and Find Full Text PDFPolycomb repressive complex 2 has a critical role in the maintenance of bivalent promoters and is often perturbed in cancer, including neuroendocrine tumors. In this study, we investigated the susceptibility of Merkel cell carcinoma (MCC), a neuroendocrine carcinoma of the skin, to inhibitors of the Polycomb repressive complex 2 catalytic subunit EZH2. We show that a subset of MCC cell lines is sensitive to EZH2 inhibitor-induced cell viability loss.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) is associated with multiple human malignancies. To evade immune detection, EBV switches between latent and lytic programs. How viral latency is maintained in tumors or in memory B cells, the reservoir for lifelong EBV infection, remains incompletely understood.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) is a gamma-herpesvirus that establishes lifelong infection in the majority of people worldwide. EBV uses epigenetic reprogramming to switch between multiple latency states in order to colonize the memory B-cell compartment and to then periodically undergo lytic reactivation upon plasma cell differentiation. This review focuses on recent advances in the understanding of epigenetic mechanisms that EBV uses to control its lifecycle and to subvert the growth and survival pathways that underly EBV-driven B-cell differentiation versus B-cell growth transformation, a hallmark of the first human tumor virus.
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