Exclusion of Superinfection or Enhancement of Superinfection in Pestiviruses—APPV Infection Is Not Dependent on ADAM17

Some viruses can suppress superinfections of their host cells by related or different virus species. The phenomenon of superinfection exclusion can be caused by inhibiting virus attachment, receptor binding and entry, by replication interference, or competition for host cell resources. Blocking attachment and entry not only prevents unproductive double infections but also stops newly produced virions from re-entering the cell post-exocytosis. In this study, we investigated the exclusion of superinfections between the different pestivirus species. Bovine and porcine cells pre-infected with non-cytopathogenic pestivirus strains were evaluated for susceptibility to subsequent superinfection using comparative titrations. Our findings revealed significant variation in exclusion potency depending on the pre- and superinfecting virus species, as well as the host cell species. Despite this variability, all tested classical pestivirus species reduced host cell susceptibility to subsequent infections, indicating a conserved entry mechanism. Unexpectedly, pre-infection with atypical porcine pestivirus (APPV) increased host cell susceptibility to classical pestiviruses. Further analysis showed that APPV can infect SK-6 cells independently of ADAM17, a critical attachment factor for the classical pestiviruses. These results indicate that APPV uses different binding and entry mechanisms than the other pestiviruses. The observed increase in the susceptibility of cells post-APPV infection warrants further investigation and could have practical implications, such as aiding challenging pestivirus isolation from diagnostic samples.