Highly activated RNA silencing via strong induction of dicer by one virus can interfere with the replication of an unrelated virus

Significance RNA silencing-mediated virus interference or cross-protection generally occurs between closely related strains of a single virus species. Here, we show strong virus interference between unrelated RNA viruses in the filamentous ascomycetous fungus, Cryphonectria parasitica . Lateral transmission and replication of a totivirus with an undivided dsRNA genome was severely inhibited by a silencing suppressor deletion mutant of the prototype hypovirus with a positive-strand RNA genome or the prototype mycoreovirus with an 11-segmented dsRNA genome, and even by transgenic expression of hairpin RNA of an endogenous fungal gene. This interference required high-level expression of the key RNA silencing gene, dicer-like 2 ( dcl2 ), but not necessarily argonaute-like 2 ( agl2 ). This study provides insight into broad-spectrum virus control.