Determinants of heterospecific phase separation in negative-strand RNA viruses
Negative-sense RNA viruses (NSVs) like Ebola and Lassa viruses pose significant global health risks, necessitating not only the development of novel broad-spectrum antivirals beyond traditional nucleoside analogs to prevent drug resistance but also to identify novel targets.
These viruses replicate their genomes in membrane-less viral inclusion bodies, which are biomolecular condensates of viral and cellular proteins and RNA formed by liquid-liquid phase separation. Currently, it is poorly understood why only specific cellular and viral proteins are recruited into these condensates and what role the viral RNA genome plays in their recruitment.
We hypothesize that general principles govern the association of essential factors to form inclusion bodies. To uncover these mechanisms, we will develop and use live-cell Click labeling of viral RNA based on our TriPPPro-technology to visualize, purify, and analyze inclusion bodies and their components.
Understanding the mechanisms by which inclusion bodies are formed will facilitate the development of novel antiviral inhibitors that disrupt inclusion body formation, offering new strategies against both known and emerging viral threats, including future threats like "Disease X."