Long-term-infected telomerase-immortalized endothelial cells: a model for Kaposi's sarcoma-associated herpesvirus latency in vitro and in vivo.

Journal of Virology
Feng-Qi AnRolf Renne

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease. Most KS tumor cells are latently infected with KSHV and are of endothelial origin. While PEL-derived cell lines maintain KSHV indefinitely, all KS tumor-derived cells to date have lost viral genomes upon ex vivo cultivation. To study KSHV latency and tumorigenesis in endothelial cells, we generated telomerase-immortalized human umbilical vein endothelial (TIVE) cells. TIVE cells express all KSHV latent genes 48 h postinfection, and productive lytic replication could be induced by RTA/Orf50. Similar to prior models, infected cultures gradually lost viral episomes. However, we also obtained, for the first time, two endothelial cell lines in which KSHV episomes were maintained indefinitely in the absence of selection. Long-term KSHV maintenance correlated with loss of reactivation in response to RTA/Orf50 and complete oncogenic transformation. Long-term-infected TIVE cells (LTC) grew in soft agar and proliferated under reduced-serum conditions. LTC, but not parental TIVE cells, formed tumors in nude mice. These tumors expressed high levels of the latency-associated nuclear ...Continue Reading

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Citations

Oct 19, 2007·Archives of Virology·N CloutierL Flamand
Jun 8, 2013·Cancer Letters·Lu DaiZhiqiang Qin
Sep 25, 2010·Nature Reviews. Cancer·Enrique A MesriChris Boshoff
Jan 31, 2013·Nucleic Acids Research·Russell P DarstMichael P Kladde
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Feb 2, 2012·The Journal of Clinical Investigation·Tiffany JonesShou-Jiang Gao
Feb 26, 2016·Frontiers in Microbiology·Suhani Thakker, Subhash C Verma
Aug 26, 2015·The Journal of Endocrinology·Matthias R MeyerEric R Prossnitz
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Jun 10, 2010·PLoS Pathogens·Thomas Günther, Adam Grundhoff
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