Fig. 2

Overview of protein interactions during the LASV arenavirus life cycle in the host cell. 1 GP1 present on the viral surface binds α-dystroglycan for primary attachment. Receptors AXL, Tyro3, DC-SIGN, and LSECtin are also involved in interanalizing the LASV virion. Glycosylation of GP1 hinders neutralizing antibody binding. 2 pH-dependent GP1 binding to LAMP1 in the late endosome precedes GP2-mediated fusion. GP2 causes fusion at the endosomal membrane and deposition of viral contents into the host cytoplasm. 3 Once in the cytoplasm, RNP comprised of L protein (RdRP), NP, and vRNA initiate transcription and replication of the viral genome. Replication effiency correlates well to pathogenicity. 4 Viral transcriptional and translational products include NP, L protein, Z, and the GP1-GP2 precursor. 5 Viral proteins interfere with the host antiviral response and aid in immune evasion and supression. NP degrades dsRNA, preventing RIG-I and MDA5 recognition. 5’ and 3’ UTRs form panhandle structures with single nucleotide mismatches, inhibiting RIG-I and MDA5. Z inhibits RIG-I and MAVS association. NP also modulates IKKε and DDX3 activity, preventing establishment of an antiviral state in the host cell. NP has decoy caspace cleavage sites which decrease apoptosis. 6 GPC maturation from the GP1-GP2 precursors and transport occur in the endoplasmic reticulum and Golgi apparatus. SSP is co-translationally cleaved from GPC, and SKI-1/S1P processes GPC for maturation and formation of virions and fusions. 7 Virions assemble at the surface of the host cell and bud off from the plasma membrane with a host-derived lipid envelope. Z late domains PTAP and PPPY interact with ESCRT-1 and NEDD4 to mediate multivesicular budding