Liyuan Liu, University of Toronto

Maria Cecilia Gimenez1*, Liyuan Liu1*, Khalid Osmanov1, Nuria Verdaguer3, Mauricio Terebiznik1,2#, Diego Sebastian Ferrero3#. 1 Department of Biological Sciences, University of Toronto at Scarborough, Toronto, Ontario, Canada, PC: M1C 1A4. 2 Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada, PC: M5S 3G5. 3 Institut de Biología Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Barcelona, Spain, PC: 08028 Barcelona. * Maria Cecilia Gimenez and Liyuan Liu contributed equally to this work. # co-corresponding authors

Fighting & Responding

Infectious pancreatic necrosis (IPN) is a highly contagious disease in aquaculture. It primarily affects farmed salmonids and is caused by the Infectious Pancreatic Necrosis Virus (IPNV). Disease mortality can climb up to 90% among juveniles, and survivors often become life-long asymptomatic carriers. Disease outbreaks occur globally and cost billions in lost production, yet antiviral treatments and effective vaccines remain a major challenge worldwide. IPNV belongs to the Birnaviridae family, a group of non-enveloped viruses with a bipartite double-stranded RNA genome. The viral protein 3 (VP3) is the second most abundant structural protein of the virion with essential functions during the viral replication cycle. As such, VP3 is an attractive candidate to be targeted for the rational development of live-attenuated vaccines. VP3 contains 3 main domains D1-D2-D3. In a recent study using the birnavirus Infectious Bursal Disease Virus (IBDV), we unveiled the structure and function of the amino-terminal domain of VP3 (D1) and proved its vital role for virus viability. Since VP3 exhibits significant conservation across the family, in this study we focused on IPNV. We developed and tested an in-house IPNV reverse genetic system and engineered it to assess the role of the D1 domain in IPNV viability. Our results show a conserved critical role of the D1 domain amongst member of the Birnaviridae family, while emphasizing the potential of VP3 as a lead vaccine candidate for the rational development of live-attenuated vaccines.