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Contents - College of Medical and Dental Sciences - University of ...

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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK<br />

Pathogenesis Abstract 16<br />

DEVELOPMENT OF ANIMAL MODELS OF KSHV INFECTION AND AIDS-<br />

ASSOCIATED DISEASE BASED ON MACAQUE RHADINOVIRUSES<br />

A. Gregory Bruce 1 , Jonathan T. Ryan 1 , Courtney Gravett 1,2 , <strong>and</strong> Timothy M. Rose 1,2 ,<br />

1 Seattle Children’s Hospital Research Institute <strong>and</strong> 2 <strong>University</strong> <strong>of</strong> Washington, Seattle WA<br />

Abstract<br />

Two related viral lineages within the Rhadinovirus genus <strong>of</strong> gammaherpesviruses have<br />

been identified in macaques <strong>and</strong> other Old World non-human primates. In macaques,<br />

the prototypes <strong>of</strong> these lineages were first identified in the rhesus macaque (Macaca<br />

mulatta); retroperitoneal fibromatosis-associated herpesvirus (RFHVMm) <strong>and</strong> rhesus<br />

rhadinovirus (RRV) members <strong>of</strong> the Rhadinovirus-1 (RV1) <strong>and</strong> RV2 lineages, respectively.<br />

Each macaque species is host to a distinct pair <strong>of</strong> RV1 <strong>and</strong> RV2 rhadinoviruses,<br />

distinguishable by molecular sequence. Both RV1 <strong>and</strong> RV2 rhadinoviruses have been<br />

implicated in diseases in macaques that closely resemble cancers <strong>and</strong> proliferative<br />

diseases associated with KSHV in humans, including Kaposi sarcoma (KS), lymphoma<br />

<strong>and</strong> multicentric Castleman’s disease. Thus, the characterization <strong>of</strong> the macaque<br />

rhadinoviruses, including the development <strong>of</strong> specific reagents <strong>and</strong> assays that enable<br />

the evaluation <strong>of</strong> their biology <strong>and</strong> life cycles, is an important aspect in the development<br />

<strong>of</strong> KSHV-related macaque models <strong>of</strong> disease. We have developed protocols for<br />

experimental infection <strong>of</strong> macaques with both RV1 <strong>and</strong> RV2 macaque rhadinoviruses, <strong>and</strong><br />

are developing reagents <strong>and</strong> analytical approaches to follow the resulting infections <strong>and</strong><br />

host responses to infection in vivo. We will present the current status <strong>of</strong> the first small<br />

pilot study examining the experimental infection <strong>of</strong> naïve macaques with infectious<br />

rhadinoviruses from saliva <strong>of</strong> infected macaques <strong>and</strong> subsequent chemical <strong>and</strong> viral<br />

treatments to activate virus by inducing immunosuppression. These studies will provide<br />

the groundwork for establishing relevant animal models <strong>of</strong> human disease associated<br />

with KSHV.<br />

Presenting author Email: greg.bruce@seattlechildrens.org<br />

38

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