| Project Detail |
Kaposi’s sarcoma and RNA-binding proteins: from virus biology to targeted therapies
Kaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma, a type of cancer in the skin and the gastrointestinal tract, and two lymphomas: multicentric Castleman’s disease and primary effusion lymphoma. KSHV is a DNA virus that establishes a lifelong latent and persistent infection in endothelial and B cells. Reactivation produces new viral particles allowing transmission to other individuals. Insight into KSHV infection and pathogenesis will help develop targeted antiviral drugs. Funded by the Marie Sklodowska-Curie Actions programme, the KSHV-RBPome project will investigate the role of viral and host RNA-binding proteins (RBPs) in the latent infection and reactivation of KSHV. Researchers aim to generate a comprehensive catalogue of RBPs affecting the virus and to develop targeted antivirals against viral RBPs using RNA-based technologies.
Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human ?-herpesvirus, is the cause of Kaposi’s Sarcoma (KS), primary effusion lymphoma and multicentric Castlemans disease with no effective therapies. Like other herpesviruses, KSHV has a latent cycle with limited gene expression and a lytic cycle with expression of most viral genes and production of infectious viral particles. RNA-binding proteins (RBP) play key roles in RNA biology, including expression, export, stability, processing and translation. Previous reports showed that RBPs can function as proviral or antiviral. Viruses also express viral RBPs. There are no reports investigating the role of RBPs during infection with DNA viruses. Here we aim to determine the scope of host and viral RBPs involved in KSHV latent infection and reactivation. To do so, we will employ a multidisciplinary approach that combines cutting edge methods of molecular biology and virology with next generation technologies to discover cellular RBPs that directly interact with viral RNA and regulate KSHV infection and tumorigenesis. We expect also to discover novel viral RBPs involved in KSHV infection and pathogenesis. The outcome of this project will be a comprehensive census of RBPs with antiviral, proviral and pro-oncogenic activities. In the short-term, the knowledge obtained will facilitate the development of biotechnological applications to exploit the function of RBPs in RNA biology, including RNA visualization, expression and translation. In the long-term, the proviral RBPs could be targeted to develop host-based antivirals. Therefore, this project contributes to the EU global challenge of Health and the EU Mission Cancer. To ensure the successful outcome of this project, I will contribute with my experience in molecular virology and my supervisors will train me in system-wide profiling of RBPs and cutting-edge methods in virology, ensuring the appropriate transfer of knowledge among the participants. |
