title: Experimental transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) to SCID-hu Thy/Liv mice.
abstract: 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.
authors.affiliation: Department of Microbiology, University of California, San Francisco, California 94143, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dittmer
authors.forename: C
authors.initials: C
authors.lastname: Stoddart
authors.forename: R
authors.initials: R
authors.lastname: Renne
authors.forename: V
authors.initials: V
authors.lastname: Linquist-Stepps
authors.forename: M E
authors.initials: ME
authors.lastname: Moreno
authors.forename: C
authors.initials: C
authors.lastname: Bare
authors.forename: J M
authors.initials: JM
authors.lastname: McCune
authors.forename: D
authors.initials: D
authors.lastname: Ganem
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000635:transmission* / Q000821:virology*; D019288:Herpesvirus 8, Human; D006801:Humans; D051379:Mice; D016513:Mice, SCID