last updated April 2013
Hijacking the nucleus
Borna disease virus infects and remains in the nucleus of host cells by binding to the cell’s DNA scaffolding proteins
The nucleus is an inhospitable environment for an RNA virus. Virus particles risk being exported along with host mRNA, and when the nuclear membrane dissolves, they face being scattered throughout the cell. Borna disease viruses (BDV) are the only known RNA viruses that can reside in the nucleus. Now, researchers in Japan have shown that BDV occupies this difficult environment by integrating itself into the scaffolding that supports its host’s chromosomes1.
Tomonaga’s team used microscopy to reveal how BDV builds its viral factories — clusters of host cellular machinery co-opted to replicate viral particles — in the nucleus. BDV binds to histones, part of the scaffolding that organizes the long strands of DNA into compact chromosomes. HMGB1, a hijacked host protein that remodels the scaffolding, then binds BDV to chromosomes and helps to copy it. From there, BDV hitches a ride into any daughter cells when the cell replicates.
Understanding how BDV works will help researchers design future studies to prevent or control infection. BDV infects the brain cells of mammals and birds, literally driving its victims crazy by producing symptoms that resemble neurological disorders. Horses with BDV sometimes self-inflict head injuries, or starve themselves to death. The virus can also infect humans, but its effects are still being studied.