Comparative and applied studies of virulence and immuno-escape of an emerging ranavirus pathogen in the amphibian Xenopus model (43.12)

Abstract

Abstract Ranaviruses (RV), family Iridoviridae, have become increasingly prevalent pathogens of amphibians around the world, and are possibly involved in the worldwide decline of amphibian populations. Nonetheless, RVs have not yet been studied as intensively as other large DNA viruses. We have established the frog Xenopus as an important experimental model to study viral pathogenicity and host defenses against RVs such as Frog virus 3 (FV3), and evaluate the contribution of immunocompromised animals in the dissemination of the diseases. To evaluate the role of putative viral genes involved in virulence and immune evasion, we are currently developing a method to systematically knockout (KO) putative virulence genes by site-specific integration of a selectable fluorescent marker into the FV3 genome. Susceptible Xenopus larvae will provide an ideal model to evaluate the impact of KOs on in vivo virus load, host mortality and the induction of pro-inflammatory genes. Normal and immunocompromised adult frogs will be used to investigate pathogenicity and ability of KOs to evade adaptive immunity. These studies will help elucidate the interplay between virulence genes and host immune defenses and may reveal original mechanisms of host-pathogen interaction that may be relevant not only to amphibians and other lower vertebrates, but also to humans.