Development of reverse genetics systems and investigation of host response antagonism and reassortment potential for Cache Valley and Kairi viruses, two emerging orthobunyaviruses of the Americas

摘要

Author summary Cache Valley and Kairi viruses (CVV and KRIV; Peribunyaviridae, Orthobunyavirus) are important animal pathogens of the Americas. In this study we developed reverse genetics systems to study and manipulate viral genomes of both viruses. Viral genomes were mutated to prevent the expression of the NSs protein, a key virulence factor and antagonist of the type 1 interferon (IFN) system. Replication studies in IFN producing cell lines showed slower growth of the NSs-deletion carrying viruses compared to wild type virus. In contrast, in IFN-deficient cell lines growth of both viral types was comparable, highlighting the role of NSs as an IFN antagonist in both CVV and KRIV. We also demonstrated using genetic studies that CVV and KRIV are unlikely to combine by reassortment to form novel viruses at least for one combination tested here, and propose that such recombinant viruses would be suitable live attenuated vaccine candidates.