NON-HUMAN PRIMATE MODEL OF KAPOSI?S SARCOMA-ASSOCIATED HERPESVIRUS INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kaposi's sarcoma associated herpesvirus (KSHV) associates with Kaposi's sarcoma (KS), pleural effusion lymphomas (PEL), and multicentric Castleman's disease (MDC). Despite this significant human health problem, KSHV studies are greatly hampered by the lack of animal model. In here, we report the successful zoonotic transmissions of a KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate, which significantly recapitulates important aspects of KSHV infection in human. Marmosets intravenously inoculated with recombinant KSHV, called rKSHV.219, rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. In addition, KSHV DNA and latent nuclear antigen protein (LANA) were readily detected from the peripheral blood mononuclear cells (PBMCs) and various tissues of infected marmosets at multiple time points. As seen with other immunosuppressant drug that represses KSHV-infected cell growth8 and inhibits the progression of dermal KS in transplant recipients, FK506 immunosuppressant treatment led to a significant reduction of KSHV persistent infection in vivo. Furthermore, marmosets infected with rKSHV.291 by the oral route also seroconverted and were positive for viral DNA in their PBMCs. Remarkably, an orally infected marmoset developed the KS-like skin lesion with characteristic spindle cells and infiltrating leukocytes that was also positive to the KSHV DNA and K8.1 glycoprotein. AIDS related.