Kaposi's Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis.
Judith M Fontana, Justin G Mygatt, Katelyn L Conant, Chris H Parsons, Johnan A R Kaleeba
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引用次数: 4
Abstract
KSHV is the etiologic agent for Kaposi's sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/ α -MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF- κ B activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF- κ B, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals.
期刊介绍:
Journal of Skin Cancer is a peer-reviewed, Open Access journal that publishes clinical and translational research on the detection, diagnosis, prevention, and treatment of skin malignancies. The journal encourages the submission of original research articles, review articles, and clinical studies related to pathology, prognostic indicators and biomarkers, novel therapies, as well as drug sensitivity and resistance.