Influence of RNA binding on the structure and functionality of Borna disease virus matrix protein

Borna disease virus (BDV) has been used as a model system to investigate and understand persistent viral infections of the brain. Known hosts of BDV range from rodents to non-human primates and recently it was shown that the virus is responsible for the first endogenized non-retroviral virus-derived elements in mammalian genomes. BDV is the only member of the family of Bornaviridae that belongs to the order Mononegavirales, which includes among others the viruses Marburg, Ebola and Rabies.

BDV has the smallest genome among all known negative stranded non-segmented RNA viruses, with a size of 8.9 kb, encoding for six proteins. The matrix protein of BDV (BDVM), a 16.2 kDa protein that forms homotetramers and octamers, is associated with virus assembly and budding and may also be associated with the regulation of the viral ribonucleoprotein activity. Recently, we have shown that BDVM binds single stranded RNA (Neumann et al., 2009).

To further investigate the structural and functional influence of RNA binding on BDVM, we have mutated the specific RNA binding site to create the BDVM variant H112W. This variant shows a previously unknown dodecameric oligomerization state and altered RNA binding properties. Cell-based assays of recombinant viruses harbouring these mutations showed potent growth attenuation and an atypical cytoplasmic accumulation in Vero cells.