The regulation of persistent Borna disease virus infection by RNA silencing factors in human cells

Viral infection induces diverse cellular immune responses. Some viruses induce the production of antiviral cytokines, alterations of endogenous gene expression, and apoptosis; however, other viruses replicate without inducing such responses, enabling them to persistently infect cells. Infection by Borna disease virus type 1 (BoDV-1) can result in fatal immune-mediated encephalitis, including in humans, yet infection of cells in vitro is generally persistent. The regulatory mechanisms underlying this persistent infection remain unclear. Here, we show that an enhancer of RNA-silencing, TRBP, positively regulates BoDV RNA level in human cells. Knockdown of TRBP decreased BoDV RNA levels in persistently-infected cells, whereas overexpression of TRBP increased BoDV RNA levels. To investigate the mechanism un-derlying this phenomenon, we performed immunoprecipitation assays and found that TRBP interacts with BoDV RNA. Furthermore, we performed cell fractionation, which revealed that persistent infection with BoDV does not alter the localization of TRBP and other RNA silencing factors in cells. Our results showed the regulation of persistent BoDV infection by RNA-silencing factors in human cells.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

Viral infection can induce diverse cellular immune responses. In the case of Borna disease virus type 1 (BoDV-1), infection can lead to fatal immune-mediated encephalitis, but in vitro infection is usually persistent. This study shows that TRBP, an enhancer of RNA-silencing, positively regulates BoDV RNA levels in human cells. The interaction between TRBP and BoDV RNA plays a role in regulating persistent BoDV infection.