Interferon and TLR genes, but not endogenous bornavirus-like elements, limit BoDV1 replication after intracerebral infection

Borna disease virus 1 (BoDV1) is a neurotropic RNA virus, but the host factors limiting its replication in the brain are not fully understood. Endogenous bornavirus-like elements (EBLNs) have been proposed to suppress BoDV1 through piRNA-mediated mechanisms. This study aimed to evaluate the relative roles of interferon signaling, Toll-like receptor pathways, and EBLN-derived piRNAs in controlling BoDV1 replication in vivo. Neonatal mice were intracerebrally infected with a GFP-expressing recombinant BoDV1. Viral replication was analyzed in wild-type mice and knockout mice lacking the interferon-γ receptor (Ifngr1), Toll-like receptor 7 (Tlr7), or all piRNA-producing EBLNs. Viral RNA levels and infected brain cells were assessed by RT-qPCR and histological analyses. BoDV1 replication was significantly increased in Ifngr1- and Tlr7-deficient mice, indicating that interferon-γ signaling and TLR7-dependent innate immunity restrict viral growth in the brain. In contrast, deletion of EBLN-derived piRNAs had no effect on viral replication. These results demonstrate that classical immune pathways, rather than endogenous viral elements, are the primary factors limiting BoDV1 replication after intracerebral infection.
(MN)