Nature Medicine
2, 342 - 346 (1996)
doi:10.1038/nm0396-342
Lytic growth of Kaposi's sarcoma−associated herpesvirus (human herpesvirus 8) in cultureRolf Renne1, Weidong Zhong1, Brian Herndier2, Michael Mcgrath3, Nancy Abbey2, Dean Kedes1
& Don Ganem1, 4
1Howard Hughes Medical Institute and Departments of Microbiology and Medicine, University of California, San Francisco, California 94143, USA
2Department of Pathology, University of California, San Francisco, California 94143, US
3Department of Laboratory Medicine, University of California, San Francisco, California 94143, USA
4Correspondence should be addressed to D.G. Kaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, and HIV infection is known to be a major risk factor for its development1,2. However, KS can occur in the absence of HIV infection3−5 and the risk of KS development varies widely even among HIV−infected patients, with homosexual men with AIDS being 20 times more likely to develop KS than AIDS−afflicted children or hemophiliacs6. These and other data strongly suggest that a sexually transmitted agent or co−factor may be involved in KS pathogenesis7. Recently, DNA sequences corresponding to the genome of a novel member of the herpesvirus family have been identified within AIDS−KS biopsies8, and several reports indicate that these sequences are also present in all forms of HIV−negative KS (ref. 9−13). These and other findings14 suggest this new agent, referred to as KS−associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), as a candidate for the putative etiologic cofactor. However, the role of this agent in KS remains hotly debated15. Further progress in understanding its biology has been severely hampered by the lack of a cell culture system for virus growth. Here we report the development of a system for the lytic growth of this virus in a latently infected B cell line and present the first ultrastructural visualization of the virus. This system will facilitate the detailed study of the molecular biology of viral replication, the testing of antiviral drugs and the development of diagnostic tests for viral infection.
REFERENCES
- Ensoli, B., Barillari, G. & Gallo, R.C. Pathogenesis of AIDS-associated Kaposi's sarcoma. Hematol. Oncol. Clin. N. Am. 5, 281 (1991). | ISI | ChemPort |
- Ganem, D., Viruses, cytokines and Kaposi's sarcoma. Curr. Biol. 5 469 (1994). | ISI |
- Penn, I. Kaposi's sarcoma in organ transplant recipients. Transplantation 27, 8−11 (1979). | PubMed | ISI | ChemPort |
- Ziegler, J., Templeton, A.C., & Voegel, G.L. KS: A comparison of classical, endemic and epidemic forms. Semin. Oncol. 11, 47−52 (1984)
- Freidman-Kien, A., Saltzman, B.R. & Cao, Y. Kaposi's sarcoma in HIV-negative homosexual men. Lancet 335, 168−169 (1990). | Article |
- Beral, V. Epidemiology of Kaposi's sarcoma. Cancer Surv. 10, 5−22 (1991). | PubMed | ISI | ChemPort |
- Beral, V., Peterman, T., Berkelman, R. & Jaffe, H.W. Kaposi's sarcoma among persons with AIDS: A sexually transmitted infection? Lancet 335, 123−128 (1990). | Article | PubMed | ISI | ChemPort |
- Chang, Y. et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266 1865−1869 (1994). | PubMed | ISI | ChemPort |
- Moore, P. & Chang, Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma patients with and those without HIV infection. N. Engl. J. Med. 332, 1181−1185 (1995). | Article | PubMed | ISI | ChemPort |
- Huang, Y.-Q. et al. A human herpesvirus-like DNA sequence in various forms of Kaposi's sarcoma. Lancet 345, 759−761 (1995). | Article | PubMed | ISI | ChemPort |
- Ambroziak, J. et al. Herpesvirus-like sequences in HIV-infected and uninfected Kaposi's sarcoma patients. Science 268, 582−583 (1995). | PubMed | ISI | ChemPort |
- Schalling, M. et al. A role for a new herpesvirus (KSHV) in different forms of Kaposi's sarcoma. Nature Med. 1, 707−708 (1995) | Article | PubMed | ISI | ChemPort |
- Chuck, S., Grant, R.M., Katongole-Mbidde, E., Conant, M. & Ganem, D. Frequent presence of herpesviral-like DNA sequences in lesions of HIV-negative Kaposi's sarcoma. J. Infect. Dis. 173, 248−251 (1996). | PubMed | ISI | ChemPort |
- Whitby, D. et al. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet 346, 799−802 (1995). | Article | PubMed | ISI | ChemPort |
- Cohen, J., Controversy:Is KS really caused by new herpesvirus? Science 268, 1847 (1995)
- Cesarman, E., Chang, Y., Moore, P.S., Said, J.W. & Knowles, D. Kaposi's sarcoma associated herpesvirus-like DNA sequences in AIDS-related body cavity based lymphomas. N. Engl. J. Med. 332, 1186−1190 (1995). | Article | PubMed | ISI | ChemPort |
- Soulier, J. et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86, 1276−1280 (1995). | PubMed | ISI | ChemPort |
- Roizman, B. Herpesviridae: A brief introduction, in Virology, 2nd edn (ed. Fields, B.N.) 1787−1793 (Raven, New York, 1990).
- Kieff, E. Epstein-Barr virus and its replication, in Virology, 2nd edn (ed. Fields, B.N.) 1902−1903 (Raven, New York, 1990).
- zur Hausen, H., O'Neill, F.J., Freese, U.K. & Hecher, E. Persisting oncogenic herpesvirus induced by tumor promoter TPA. Nature 272 373−375 (1979).
- Luka, J., Kallin, B. & Klein, G. Induction of the Epstein-Barr virus life cycle in latently infected cells by n-butyrate. Virology 94, 228−231 (1979). | Article | PubMed | ISI | ChemPort |
- Takada, K. Crosslinking of cell surface immunoglobulin induces Epstein-Barr virus in Burkitt lymphoma lines. Int. J. Cancer 33, 27−32 (1984). | PubMed | ISI | ChemPort |
- Ben-Sasson, S. & Klein, G. Activation of Epstein-Barr virus genome by 5 aza-cytidine in latently infected human lymphoid lines. Int J. Cancer 28, 131−135 (1981). | PubMed | ChemPort |
- Countryman, J., Jenson, H., Siebel, R., Wolf, H. & Miller, G. Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency. J. Virol. 61, 3672−3679 (1987). | PubMed | ISI | ChemPort |
- Hummel, M. & Kieff, E. Mapping of polypeptides encoded by the Epstein-Barr virus genome in productive infection. Proc. Natl. Acad. Sci. USA 79 5698−5702 (1982). | PubMed | ChemPort |
- Lenhoff, R. & Summers, J. Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus. J. Virol. 68, 4565−4571 (1994). | PubMed | ISI | ChemPort |
- Moore, P. et al. Primary characterization of a herpesvirus agent associated with Kaposi's sarcoma. J. Virol. 70, 549−558 (1996). | PubMed | ISI | ChemPort |
- Church, G.M. & Gilbert, W. Genomic sequencing. Proc. Natl. Acad. Sci. USA 81, 1991−1995 (1984). | PubMed | ChemPort |
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