Fig. 2: Interaction between the nonstructural protein NSs and the host cellular machinery.

Bunyaviruses attach to host cell surfaces via various receptors and are internalized before escaping from late endosomes into the cytosol (1). After genome release, the RNA segments are either transcribed into mRNAs for protein synthesis (2) or replicated for packaging into new virions (3). Throughout the replication cycle, NSs proteins interfere with multiple host antiviral pathways (highlighted in red). ANDV Andes virus, BUNV Bunyamwera virus, CCHFV Crimean Congo hemorrhagic fever virus, cRNA complementary RNA, DABV Dabie virus, HRTV Heartland virus, IFN interferon, IKK IκB kinase, IRF IFN regulatory factor, LACV La Crosse virus, LEs late endosomes, MAVS mitochondrial antiviral-signaling protein, mtDNA mitochondrial DNA, mTOR mammalian target of rapamycin, NFκB nuclear factor kappa B, NLRP3 NOD-like receptor family pyrin domain containing 3, PKR protein kinase R, RIG-I retinoic acid-inducible gene I, ROS reactive oxygen species, RVFV Rift Valley fever virus, SAFA scaffold attachment factor A, SBV Schmallenberg virus, SFSV Sandfly fever Sicilian virus, TBK1 TANK-binding kinase 1, TOSV Toscana virus, TRAF TNF receptor-associated factor, TRIF TIR-domain-containing adapter-inducing IFN-β, vRNA viral genomic RNA. Created in part with BioRender.com.