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J Virol, June 1998, p. 4980-4988, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of Kaposin (Open Reading Frame K12) as a Human Herpesvirus 8 (Kaposi's Sarcoma-Associated Herpesvirus) Transforming Gene

Sumitra Muralidhar,1 Anne M. Pumfery,1 Morad Hassani,1 M. Reza Sadaie,1 Norio Azumi,2 Masamichi Kishishita,1 John N. Brady,3 Jay Doniger,1 Peter Medveczky,4 and Leonard J. Rosenthal1,*

Department of Microbiology and Immunology1 and Department of Pathology,2 Georgetown University Medical Center, Washington, D.C. 20007; Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 208923; and Department of Medical Microbiology and Immunology, University of South Florida, Tampa, Florida 336124

Received 17 December 1997/Accepted 2 March 1998

The recently identified human herpesvirus 8 (HHV-8, or Kaposi's sarcoma-associated herpesvirus) has been implicated in the etiology of both Kaposi's sarcoma (KS) and primary effusion (body cavity-based) lymphoma (PEL) (Y. Chang et al., Science 266:1865-1869, 1994; P. S. Moore et al., J. Virol. 70:549-558, 1996). An important feature of the association of HHV-8 with these malignancies is the expression of an abundant, latency-associated 0.7-kb transcript, T0.7 (W. Zhong et al., Proc. Natl. Acad. Sci. USA 93:6641-6646, 1996). T0.7 is found in all stages in nearly all KS tumors of different epidemiologic origin, including AIDS-associated, African endemic, and classical KS (K. A. Staskus et al., J. Virol. 71:715-719, 1997), as well as in a body cavity-based lymphoma-derived cell line, BCBL-1, that is latently infected with HHV-8 (R. Renne et al., Nat. Med. 2:342-346, 1996). T0.7 encodes a unique HHV-8 open reading frame, K12, also known as kaposin. In this study, we report that the kaposin gene induced tumorigenic transformation. Constructs with kaposin expressed either from its endogenous promoter or from a heterologous promoter induced focal transformation upon transfection into Rat-3 cells. All transformed Rat-3 cell lines containing kaposin sequences produced high-grade, highly vascular, undifferentiated sarcomas upon subcutaneous injection of athymic nu/nu mice. Tumor-derived cell lines expressed kaposin mRNA, suggesting a role in the maintenance of the transformed phenotype. Furthermore, kaposin protein was detected in transformed and tumor-derived cells by immunofluorescence and localized to the cytoplasm. More importantly, expression of kaposin protein was also detected in the PEL cell lines BCBL-1 and KS-1. These findings demonstrate the oncogenic potential of kaposin and suggest its possible role in the development of KS and other HHV-8-associated malignancies.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Georgetown University Medical Center, 3900 Reservoir Rd., NW, Washington, D.C. 20007. Phone: (202) 687-1140. Fax: (202) 687-1264. E-mail: rosenthl{at}gunet.georgetown.edu.

J Virol, June 1998, p. 4980-4988, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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