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Cell Host Microbe, Apr 15 2024, S1931-3128(24)00112-4 | https://doi.org/10.1016/j.chom.2024.03.012
The complete Kaposi sarcoma-associated herpesvirus genome induces early-onset, metastatic angiosarcoma in transgenic mice
Sang-Hoon Sin 1,4, Anthony B. Eason 1, Yongbaek Kim 2, Johann W. Schneider 3, Blossom Damania 1, Dirk P. Dittmer 1,5
1Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
2Laboratory of Veterinary Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
3National Health Laboratory Service, Division of Anatomical Pathology, Faculty of Medicine and Health Sciences, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
4Deceased
5Lead contact
Corresponding author : Dirk P. Dittmer
Abstract
Kaposi sarcoma (KS) is the most common cancer in persons living with HIV. It is caused by KS-associated herpesvirus (KSHV). There exists no animal model for KS. Pronuclear injection of the 170,000-bp viral genome induces early-onset, aggressive angiosarcoma in transgenic mice. The tumors are histopathologically indistinguishable from human KS. As in human KS, all tumor cells express the viral latency-associated nuclear antigen (LANA). The tumors transcribe most viral genes, whereas endothelial cells in other organs only transcribe the viral latent genes. The tumor cells are of endothelial lineage and exhibit the same molecular pattern of pathway activation as KS, namely phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR, interleukin-10 (IL-10), and vascular endothelial growth factor (VEGF). The KSHV-induced tumors are more aggressive than Ha-ras-induced angiosarcomas. Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-25)
- 국외 연구진
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