Abubakar, N.; Mon, H.; Fujii, T.; Fujimoto, T.; Kusakabe, T.; Hino, M.

Bombyx mori latent virus (BmLV) is a persistent RNA virus frequently detected in silkworm-derived cell lines and has been reported to interact with B. mori nucleopolyhedrovirus (BmNPV). However, whether previous BmLV exposure alters subsequent BmNPV infection in silkworm larvae remains unclear. Here, we examined how BmLV exposure history affects subsequent BmNPV infection in cultured cells and fifth-instar B. mori larvae. Persistent BmLV infection increased BmNPV-mediated reporter protein expression and BmNPV genome abundance in cultured cells, whereas short-term BmLV exposure or simultaneous BmLV and BmNPV coinfection did not reproduce the increases observed in persistently BmLV-positive cultures. In silkworm larvae (n22 strain), 24 h BmLV pre-exposure before BmNPV challenge increased BmNPV-mediated reporter protein expression and viral genome accumulation compared with BmNPV infection alone. BmLV antigenome RNA was detected in multiple larval tissues after BmLV exposure, indicating BmLV replication during the pre-exposure period. Notably, this prior BmLV exposure was associated with altered antiviral responses upon subsequent BmNPV infection. Specifically, BmLV-pre-exposed larvae showed reduced induction of Dicer-2, R2D2, and stimulator of interferon genes (STING) in the fat body. These findings indicate that prior BmLV exposure enhances subsequent BmNPV infection and is associated with attenuated induction of host antiviral genes. This study expands our understanding of how sequential viral infections shape host-virus interactions and suggests a novel approach for increasing recombinant protein production in baculovirus-based expression systems.