Bornavirus Closely Associates and Segregates with Host Chromosomes to Ensure Persistent Intranuclear Infection

SummaryBornaviruses are nonsegmented negative-strand RNA viruses that establish a persistent infection in the nucleus and occasionally integrate a DNA genome copy into the host chromosomal DNA. However, how these viruses achieve intranuclear infection remains unclear. We show that Borna disease virus (BDV), a mammalian bornavirus, closely associates with the cellular chromosome to ensure intranuclear infection. BDV generates viral factories within the nucleus using host chromatin as a scaffold. In addition, the viral ribonucleoprotein (RNP) interacts directly with the host chromosome throughout the cell cycle, using core histones as a docking platform. HMGB1, a host chromatin-remodeling DNA architectural protein, is required to stabilize RNP on chromosomes and for efficient BDV RNA transcription in the nucleus. During metaphase, the association of RNP with mitotic chromosomes allows the viral RNA to segregate into daughter cells and ensure persistent infection. Thus, bornaviruses likely evolved a chromosome-dependent life cycle to achieve stable intranuclear infection.

► BDV uses chromatin to assemble viral factories within the host cell nucleus
► BDV RNP associates with chromatin by interacting with core histones
► BDV RNP is segregated along with mitotic chromosomes into daughter cell nuclei
► HMGB1 is involved in the stability and transcription of BDV RNP in the nucleus