Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling

Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases humans. Although an exacerbated immune response relates to hantaviral pathologies, have antagonize the antiviral interferon (IFN) successfully propagate infected cells. We studied interactions of structural and nonstructural (NSs) proteins pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), non-pathogenic Prospect Hill (PHV) viruses, with human type I III IFN (IFN-I IFN-III) pathways. The NSs all three viruses inhibited RIG-I-activated IFN? promoter, while only glycoprotein precursor (GPC) PUUV, or its cleavage product Gn/Gc, nucleocapsid (N) TULV it. Moreover, GPC both PUUV antagonized promoter IFN-stimulated responsive elements (ISRE). Different viral could thus contribute inhibition a context. While strains replicated similarly, whether expressing entire truncated proteins, encoding wild protein led late expression activation genes (ISG). This, together identification particular domains different biological processes that associated cellular complex suggested IFN-I is probably not pathway be counteracted by multiple inhibitory functions.