No Two Strands Are Alike

Like bacteria, viruses have their own genome. The ends or termini of a viral RNA are especially interesting for virologists because they play an important role in reproduction and in the reaction of the innate immune system to the virus. The genetic information is reproduced when a strand of the genome is transcribed into a complementary strand of the so-called antigenome. This strand then serves as the model or template for the synthesis of a new genome.

As a result of this simple copying mechanism, the two strands are normally exact copies of each another. However, this is not the case with the Borna disease virus (BDV), which belongs to the group of negative-strand RNA viruses. When one compares the genome and the antigenome of the BDV, one finds that the two strands possess four additional nucleotides each as components of the RNA at their 3’ termini. There is no template on the complementary strand for this elongation, and the process thus cannot be explained with the standard model of reproduction.

In a new study, “Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3’ termini,” a Freiburg research group led by Dr. Urs Schneider (now Québec, Canada) at the Institute of Microbiology and Hygiene, Department of Virology, was able to demonstrate that the additional nucleotides are not transcribed from the complementary strand but from a template located within the newly synthesized viral strand.

The study describes the use of internal templates for RNA synthesis for the first time and presents a previously unknown possibility for modifying viral genome termini. The significance of genome elongation for the reproduction and pathogenesis of the BDV is not yet completely clear. However, there are indications that this mechanism serves the dual function of preserving the integrity of the genome termini and making them unidentifiable for the innate immune system. Further experimentation will be necessary to clarify the significance of the “realignment and elongation” mechanism described in the study.

In some animals (e.g., horses), the BDV establishes a terminal infection that can lead to a severe neurological illness, ending in death.

Publication: Arnold Martin, Nadja Hoefs, Josefine Tadewaldt, Peter Staeheli, Urs Schneider: “Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3′ termini.” PNAS (Proceedings of the National Academy of Sciences).

Edited by Charles Weissmann, The Scripps Research Institute, Jupiter, FL.

German Press Release