Innate Immune Evasion by Seoul Orthohantavirus Within Its Natural Reservoir

Orthohantaviruses are zoonotic, negative-sense RNA viruses maintained in persistently infected rodent reservoirs, where they cause no disease yet drive severe vascular pathology in humans. This dissertation investigates how Seoul orthohantavirus (SEOV) establishes persistence within reservoir endothelial cells while avoiding antiviral signaling that would otherwise restrict replication. Comparative infections in rat and human endothelial cells show that SEOV genomic RNAs form perinuclear microdomains in reservoir cells but remain dispersed in human cells. These virus-induced structures colocalize with the Golgi, ERGIC, ER, and mitochondria, revealing striking host-specific membrane remodeling. This remodeling reflects a fundamental divergence in SEOV’s replication strategy across host species and may underlie its evasion of the cytosolic RNA sensor RIG-I without direct antagonism. Together, these findings identify organelle remodeling as a structural mechanism supporting immune evasion and persistence in the natural host, illuminating broader principles of viral persistence, immune modulation, and hantavirus–reservoir coevolution.