RT Journal Article SR Electronic(1) A1 Hardy, Alexandra A1 Stewart, Meredith A1 Shaw, Andrew A1 Varela, Mariana A1 Wilson, Sam A1 Randall, Richard A1 Palmarini, MassimoYR 2019 T1 Species-specific restriction of Bluetongue virus replication correlates to host resilience JF Access Microbiology, VO 1 IS 1A OP SP 275 DO https://doi.org/10.1099/acmi.ac2019.po0130 PB Microbiology Society, SN 2516-8290, AB Bluetongue is a vector-borne disease of ruminants caused by bluetongue virus (BTV). BTV can infect essentially all domestic and wild ruminants but the clinical outcome of infection differs substantially between host species. Clinical disease induced by BTV, including haemorrhagic fever in severe cases, is normally evident only in sheep. Conversely, cattle are more resilient to BTV infection, as they develop high levels of viremia and can be reservoirs of infection, but rarely show clinical signs. Here, we concentrated on BTV-host cell interactions using primary cells as an experimental system. First, we determined that BTV reaches higher titres in ovine cells, compared to bovine cells although it induces comparable levels of antiviral cytokines in both cell types. Importantly, these differences are abolished by inhibiting the Jak/Stat pathway. In addition, pre-treatment with interferon (IFN) severely hampers BTV replication in bovine, but not in ovine, primary cells. These data suggest that bovine, unlike ovine, IFN-stimulated genes (ISGs) are effective in controlling BTV replication. Using a high-throughput flow cytometry approach, we screened an expression library of over 300 bovine ISGs to identify genes with antiviral properties against BTV. We have identified ∼10 bovine ISGs that negatively impact BTV replication (by at least 50%). Currently, we are assessing the sheep orthologues to the bovine ISGs of interest in order to investigate host-species differences. Our study provides novel insights on how bovine cells restrict BTV replication and could provide an intellectual framework to understand the host determinants involved in disease severity., UL https://www.microbiologyresearch.org/content/journal/acmi/10.1099/acmi.ac2019.po0130