The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1857/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 12, December 20, 1999 1857-1868

Original Article

Experimental Transmission of Kaposi's Sarcoma–Associated Herpesvirus (Kshv/Hhv-8) to Scid-Hu Thy/Liv Mice

D. Dittmerb,c, C. Stoddarta,d, R. Renneb,c, V. Linquist-Steppsa,d, M.E. Morenoa,d, C. Barea,d, J.M. McCunea,d, and D. Ganemb,c

a Departments of Microbiology and Medicine, University of California, San Francisco, California 94143
b Department of Microbiology and Immunology and Department of Medicine, University of California, San Francisco, California 94143
c Howard Hughes Medical Institute, University of California, San Francisco, California 94143
d Gladstone Institute of Virology and Immunology, San Francisco, California 94110
Dept. of Microbiology and Immunology, University of California, 513 Parnassus Ave., HSE403, San Francisco, CA 94143-0414.415-476-0939415-476-2826

ganem{at}socrates.ucsf.edu

Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) is a novel human lymphotropic herpesvirus linked to several human neoplasms. To date, no animal model for infection by this virus has been described. We have examined the susceptibility of C.B-17 scid/scid mice implanted with human fetal thymus and liver grafts (SCID-hu Thy/Liv mice) to KSHV infection. KSHV virions were inoculated directly into the implants, and viral DNA and mRNA production was assayed using real-time quantitative polymerase chain reaction. This revealed a biphasic infection, with an early phase of lytic replication accompanied and followed by sustained latency. Ultraviolet irradiation of the inoculum abolished all DNA- and mRNA-derived signals, and infection was inhibited by ganciclovir. Viral gene expression was most abundant in CD19+ B lymphocytes, suggesting that this model faithfully mimics the natural tropism of this virus. Short-term coinfection with HIV-1 did not alter the course of KSHV replication, nor did KSHV alter levels of HIV-1 p24 during the acute phase of the infection. Although no disease was evident in infected animals, SCID-hu Thy/Liv mice should allow the detailed study of KSHV tropism, latency, and drug susceptibility.

Key Words: Kaposi's sarcoma–associated herpesvirus • KSHV • SCID-hu • transmission • real-time PCR

Abbreviations used in this paper: HHV, human herpesvirus; KSHV, Kaposi's sarcoma–associated herpesvirus; PEL, primary effusion lymphoma; RT, reverse transcriptase.

© 1999 The Rockefeller University Press


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