Baculovirus-induced fast-acting innate immunity as an antiviral strategy against Foot-and-mouth Disease Virus

MOLINA GN; OTERO I; GRAVISACO MJ; AMALFI S; GISMONDI MI; TABOGA OA; MOLINARI, P.

Bangkok

Congreso; 2019 Meeting of the Global Foot-and-mouth Disease Research Alliance; 2019

GFRA

Baculoviruses are a family of DNA viruses that infect insects. The inoculation of budded virions(BVs) of the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) in mice induces a strong innate immune response and stablishes an antiviral status that protected them against a challenge with foot-and-mouth disease virus (FMDV) at 3 h and 3 d post-inoculation. The vaccines for FMDV take between 4 and 7 days to develop protective immune response, so this strategy could be useful to reduce this immunological window. In this work, we studied the immunological mechanisms involved in the induction of this antiviralstatus in mice and evaluated the possibility to employ this technology in pigs.Firstly, we studied the role of the main antiviral effectors of the innate immunity in mice. Type I IFNs demonstrated to be a key factor to achieve effective protection in this model since IFNAR1-/- mice treated with BVs died after a lethal challenge with FMDV A/Arg/01. On the other hand, the depletion of NK cells in C57BL/6 mice before the treatment with BVs and the challenge with FMDV showed that these population is necessary both for the production ofIFN-ã and to avoid the development of the disease.Secondly, we evaluated the effects of BVs in porcine immune cells. The treatment of porcine peripheral blood mononuclear cells (PBMCs) with BVs induced IFN-á mediated antiviral activity in pigs. Moreover, the intravenously inoculation of BVs in pigs promoted the production of IFNs that were detected in sera during the first 9 hours. The profile of antiviral mediators inducedby BVs was able to protect porcine non immune cells (LFBK) against an infection with FMDV.Finally, we studied if it is possible to optimize the immune response elicited with BVs and showed that the pseudotyping of BVs with G glycoprotein of Vesicular Stomatitis Virus, but not the enrichment of the BV genome with CpG motifs for swine, improved its capacity to induce IFN-á production in porcine PBMCs.The results presented in this work suggest that BV of AcMNPV is a promising agent to develop antiviral strategies against FMDV in pigs, and that it is possible to improve biotecnologically this tool.