Viral Hijacking of the Nucleolar DNA-Damage Response Machinery: A Novel Mechanism to Regulate Host Cell Biology

Summary

This research reveals how dangerous viruses like Hendra and Nipah can hijack cellular machinery to help them reproduce more effectively. The study shows that these viruses target a specific cellular process involved in DNA repair, which helps them take over infected cells. This finding is important because: • It helps us better understand how dangerous viruses cause disease • It could lead to new treatments targeting this viral mechanism • It provides insight into basic cell biology processes • It may help predict how similar viruses behave • It demonstrates a previously unknown way that viruses can manipulate cells

Background

Recent landmark studies indicate that the nucleolus plays key roles in stress responses including the DNA-damage response (DDR). The DDR involves interactions of components of the DDR machinery including NBS1 with the sub-nucleolar protein Treacle, a key mediator of ribosomal RNA (rRNA) transcription and processing, implicated in Treacher-Collins syndrome.

Objective

To investigate how the matrix (M) proteins of Hendra virus and Nipah virus target Treacle to inhibit its function and silence rRNA biogenesis.

Results

The study found that Henipavirus M proteins target Treacle to inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicking NBS1-Treacle interaction during a DDR. Inhibition of Treacle expression/function enhanced henipavirus production.

Conclusion

The data identify a novel mechanism for viral subversion of host cell biology by appropriating the nucleolar DDR and represent the first direct intra-nucleolar function for proteins of any mononegavirus.
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