Looking for the Target Cell of Kaposi's Sarcoma-Associated Herpesvirus (original) (raw)
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Journal of Investigative Dermatology, 2006
In order to gain further insight on the role of Kaposi's sarcoma-associated herpesvirus (KSHV) in classic and endemic Kaposi's sarcoma (KS) pathogenesis, we aimed to determine (i) whether KSHV is detectable in peripheral blood mononuclear cells (PBMCs), (ii) which PBMCs subpopulation harbor the virus, (iii) which clinical, histologic, and immunologic parameters are associated with KSHV viremia in a population of classic and endemic KS. KSHV viremia and various immunologic parameters were screened on 81 patients. KSHV viremia was positive in 58% of the patients. KSHV was detected in B cells, T cells, and monocytes. CD34 þ cells depleted in circulating endothelial cells (CECs) were never infected and 50% of the patients tested had CECs infected by KSHV. We observed a significant increase of IL-2 and IFN-g production by CD4 T cells and an increase of IFN-g production by CD8 T cells compared to control patients. KS progression (P ¼ 0.001) and KS staging (P ¼ 0.03) were significantly and independently associated with positive KSHV viremia. Our results show that there is no specific immunosuppression in classic or endemic KS. We showed that KSHV can be detected within CECs and that KSHV viremia could be an indicator of circulating mature or precursor spindle cells.
The kaposi’s sarcoma associated herpesvirus: a model for viral oncogenesis
2002
Kaposi´s sarcoma (KS) is the most common tumor arising in HIV-infected patients and remains a significant cause of morbidity and mortality among the AIDS population in the developing world. The recent discovery of the etiologic agent of KS, the Kaposi´s sarcoma associated herpesvirus (KSHV), has invigorated new awareness of this unique neoplasm. Indeed, examination of the KSHV genome has revealed numerous genes that may contribute to the development of the spindle cell, the dominant cell in KS lesions. Here the authors survey the current knowledge on how KSHV-encoded genes play integral roles in transformation, cell survival, and neoangiogenesis through the transduction of signals from viral-encoded genes to the host cell nucleus. These signaling pathways likely affect the expression of cellular genes involved in KS pathogenesis. Since signaling pathways have proven to be successful drug targets in the past and their role in Kaposi´s sarcoma is becoming apparent, viral-encoded survival genes are emerging targets for the development of drug research. It is therefore of utmost importance to further define their involvement in KS pathogenesis.
Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma
Microbes and Infection, 2000
Kaposi's sarcoma-associated herpesvirus (KSHV) is present in all epidemiologic forms of Kaposi's sarcoma (KS). The KSHV genome contains several open reading frames which are potentially implicated in the development of KS. Some are unique to KSHV; others are homologous to cellular genes. The putative role of these genes in the genesis of KS is discussed. © 2000 Éditions scientifiques et médicales Elsevier SAS human herpesvirus 8 / KSHV / rhadinovirus / Kaposi's sarcoma / cell transformation * Correspondence and reprints.
Kaposi sarcoma-associated herpesvirus (KSHV): Molecular biology and oncogenesis
2009
Kaposi sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA herpesvirus belonging to the c-herpesvirinae subfamily. KSHV has been associated with the development of three neoplastic diseases: Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). In this review, we discuss the three KSHV-associated malignancies, KSHV genome, latent and lytic aspects of the viral lifecycle, putative viral oncogenes, as well as therapeutic regimens used for the treatment of KS, PEL, and MCD.
PloS one, 2008
Background. The cellular reservoirs of Kaposi's sarcoma-associated herpesvirus (KSHV) and the exact nature of the putative KSHV-infected circulating precursor of spindle cells of Kaposi's sarcoma (KS) still remain poorly defined. Because KS spindle cells are thought to be of endothelial origin, and because mature endothelial cells do not sustain persistent KSHV-infection, our attention was focalized on circulating hematopoietic precursors able to differentiate into endothelial lineage. Methods and Findings. Late endothelial progenitor cells (late-EPCs) were cultured from the peripheral blood mononuclear cells of 16 patients with classic KS. The presence and load of KSHV genomes were analyzed by real-time polymerase chain reaction in DNA extracted from cells and supernatants of late-EPC cultures obtained from 7 patients. Endothelial colonies cultured from the peripheral blood of KS patients were found to satisfy all requisites to be defined late-EPCs: they appeared from the CD14negative fraction of adherent cells after 11-26 days of culture, could be serially expanded in vitro, expressed high levels of endothelial antigens but lacked leukocyte markers. Late-EPC cultures were found to harbor KSHV-DNA at variable levels and to retain the virus after multiple passages in cells as well as in supernatants, suggesting that a quote of KSHV lytic infection may spontaneously occur. Lytic phase induction or hypoxia could amplify virus release in supernatants. Conclusion. Our results suggest that circulating endothelial progenitors from KS patients are KSHV-infected and support viral productive replication and may therefore represent potential virus reservoirs and putative precursors of KS spindle cells.
Kaposi sarcoma herpesvirus pathogenesis
Philosophical Transactions of the Royal Society B: Biological Sciences, 2017
Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its ...