Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) was first identified in Kaposi's sarcoma (KS) lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA) were readily detected in the peripheral blood mononuclear cells (PBMCs) and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells.
Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8), the most recently identified human tumor-inducing virus, has been linked to Kaposi's sarcoma, pleural effusion lymphomas and multicentric Castleman's disease. In fact, KSHV accounts for a large proportion of the cancer deaths in Africa. Further, the incidence of KSHV in the US and Europe has greatly increased due to the AIDS pandemic. Despite these pressing human health problems, studies of KSHV infection are greatly hampered by the lack of cell culture and animal models. To address this serious need, we set out to develop an animal model for KSHV infection. In this manuscript, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj), a New World primate. Our study demonstrates that experimental KSHV infection of the common marmoset is highly analogous to its infection of humans, including the means of infection, sustained serological responses, latent infection of PBMCs, virus persistence, and KS-like skin lesion development, although the latter was infrequent in experimental KSHV infections. This model thus provides a unique opportunity to dissect the molecular mechanisms of KSHV infection, persistence, and pathogenesis directly in primates.