KSHV/HHV-8 and HIV infection in Kaposi's sarcoma development |
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Authors: | Pawan Pyakurel Fatemeh Pak Amos R Mwakigonja Ephata Kaaya Peter Biberfeld |
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Institution: | (1) Immunopathology Lab., Department of Pathology and Oncology, Karolinska Institutet, 171-76 Solna, Stockholm, Sweden;(2) Muhimbili University College of Health Sciences, P. O. Box 65023, Dar-Es-Salaam, Tanzania |
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Abstract: | Kaposi's sarcoma (KS) is a highly and abnormally vascularized tumor-like lesion affecting the skin, lymphnodes and viscera,
which develops from early inflammatory stages of patch/plaque to late, nodular tumors composed predominant of spindle cells
(SC). These SC are infected with the Kaposi's sarcoma-associated herpesvirus or human herpesvirus-8 (KSHV/HHV-8). KS is promoted
during HIV infection by various angiogenic and pro-inflammatory factors including HIV-Tat. The latency associated nuclear
antigen type 1 (LANA-1) protein is well expressed in SC, highly immunogenic and considered important in the generation and
maintenance of HHV-8 associated malignancies. Various studies favour an endothelial origin of the KS SC, expressing "mixed"
lymphatic and vascular endothelial cell markers, possibly representing hybrid phenotypes of endothelial cells (EC). A significant
number of SC during KS development are apparently not HHV8 infected, which heterogeneity in viral permissiveness may indicate
that non-infected SC may continuously be recruited in to the lesion from progenitor cells and locally triggered to develop
permissiveness to HHV8 infection. In the present study various aspects of KS pathogenesis are discussed, focusing on the histopathological
as well as cytogenetic and molecular genetic changes in KS. |
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