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Journal of Virology, October 2004, p. 11108-11120, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11108-11120.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Lytic Replication-Defective Kaposi's Sarcoma-Associated Herpesvirus: Potential Role in Infection and Malignant Transformation

Jian-Hong Deng,^1,2 Yan-Jin Zhang,^1,2, Xin-Ping Wang,^1,2, and Shou-Jiang Gao^1,2,3,4,5*

Tumor Virology Program, Children’s Cancer Research Institute,¹ Departments of Pediatrics,² Microbiology and Immunology,³ Medicine,⁴ San Antonio Cancer Institute, The University of Texas Health Science Center at San Antonio, San Antonio, Texas⁵

Received 13 April 2004/ Accepted 27 May 2004

Defective viruses often have pivotal roles in virus-induced diseases. Although Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), defective KSHV has not been reported. Using differential genetic screening methods, we show that defective KSHV is present in KS tumors and PEL cell lines. To investigate the role of defective viruses in KSHV-induced pathogenesis, we isolated and characterized a lytic replication-defective KSHV, KV-1, containing an 82-kb genomic deletion of solely lytic genes. Cells harboring KV-1 escaped G₀/G₁ apoptosis induced by spontaneous lytic replication occurred in cells infected with regular KSHV but maintained efficient latent replication. Consequently, KV-1-infected cells had phenotypes of enhanced cell proliferation and transformation potentials. Importantly, KV-1 was packaged as infectious virions by using regular KSHV as helpers, and KV-1-like variants were detected in cultures of two of five KSHV cell lines and 1 of 18 KS tumors. These results point to a potential role for defective viruses in the regulation of KSHV infection and malignant transformation.

Present address: Eastern Virginia Medical School, Norfolk, VA 23501.

Present address: University of Illinois, Chicago, IL 60612.

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• Ye, F.-C., Zhou, F.-C., Xie, J.-P., Kang, T., Greene, W., Kuhne, K., Lei, X.-F., Li, Q.-H., Gao, S.-J. (2008). Kaposi's Sarcoma-Associated Herpesvirus Latent Gene vFLIP Inhibits Viral Lytic Replication through NF-{kappa}B-Mediated Suppression of the AP-1 Pathway: a Novel Mechanism of Virus Control of Latency. J. Virol. 82: 4235-4249 [Abstract] [Full Text]