Pseudotyped zoonotic thogotoviruses exhibit broad entry range in mammalian cells

This study investigated the entry mechanisms and cell tropism of zoonotic thogotoviruses by characterizing the envelope glycoproteins (GPs) of Thogoto virus (THOV), Dhori virus (DHOV), Bourbon virus (BRBV), and Sinu virus (SINV). Using a combination of cell–cell fusion assays and three complementary pseudotyping systems such as lentiviral, influenza A virus–based, and vesicular stomatitis virus (VSV)-based vectors, the authors systematically evaluated GP functionality and host range. All four thogotovirus GPs mediated pH-dependent membrane fusion, consistent with endosomal entry via class III fusion proteins. Lentiviral and influenza-based pseudotypes demonstrated that these GPs support entry into a broad spectrum of mammalian cell lines from multiple species, indicating the likely use of a conserved or ubiquitous receptor. Replication-competent VSV pseudotypes bearing DHOV or THOV GPs enabled multi-round infection and revealed efficient entry into human hepatocyte, neuronal, alveolar epithelial, and intestinal epithelial models, including primary and stem cell-derived cultures. Although pseudotyping efficiencies varied among vector systems and GPs, the overall findings highlight the promiscuous entry capacity of thogotoviruses. Collectively, the study establishes robust pseudotyping platforms for thogotovirus research and underscores the substantial zoonotic and tissue tropism potential of this underexplored group of orthomyxoviruses.
(TMR)