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Enhanced polymerase activity confers replication competence of Borna disease virus in mice

Andreas Ackermann

Daniela Kugel

Department of Virology, University of Freiburg, D-79104 Freiburg, Germany

Correspondence
Peter Staeheli
peter.staeheli{at}uniklinik-freiburg.de
Urs Schneider
urs.schneider{at}uniklinik-freiburg.de

We previously showed that mouse adaptation of cDNA-derived Borna disease virus (BDV) strain He/80_FR was associated exclusively with mutations in the viral polymerase complex. Interestingly, independent mouse adaptation of non-recombinant He/80 was correlated with different alterations in the polymerase and mutations in the viral glycoprotein. We used reverse genetics to demonstrate that changes in the polymerase which improve enzymatic activity represent the decisive host range mutations. The glycoprotein mutations did not confer replication competence in mice, although they slightly improved viral performance if combined with polymerase mutations. Our findings suggest that the viral polymerase restricts the host range of BDV.

These authors contributed equally to this work.

Pictures of brain sections from infected mice stained with a mAb directed against the BDV nucleoprotein are available with the online version of this paper.