The mechanism underlying the organization of Borna disease virus inclusion bodies is unique among mononegaviruses

Hirai, Yuya; Tomonaga, Keizo; Horie, Masayuki

Inclusion bodies (IBs) are characteristic biomolecular condensates organized by mononegaviruses. Here, we characterize the IBs of Borna disease virus 1 (BoDV-1), a unique mononegavirus that forms IBs in the nucleus, in terms of liquid-liquid phase separation (LLPS). The BoDV-1 phosphoprotein (P) alone induces LLPS and the nucleoprotein (N) is incorporated into the P droplet in vitro. In contrast, co-expression of N and P is required for the formation of IB-like structure in cells. Furthermore, while BoDV-1 P binds to RNA, an excess amount of RNA dissolves the liquid droplets formed by N and P. Notably, the N-terminal intrinsically disordered region of BoDV-1 P is essential to drive LLPS and bind to RNA, suggesting that both abilities could compete with one another. These features are unique among mononegaviruses, and thus this study will contribute to a deeper understanding of LLPS-driven organization and RNA-mediated regulation of biomolecular condensates.