Human cells possess a previously unknown first line of defence against viral infection: a sticky molecular web that physically traps viral genomes. Research jointly led by the MRC-University of Glasgow Centre for Virus Research and the University of Dundee's MRC Protein Phosphorylation and Ubiquitylation Unit shows that a protein called ZNFX1, which scans the cell for foreign nucleic acids, responds to viral RNA by building a web of ubiquitin chains around it, quarantining the intruder.
The webs are a holding action rather than a cure. They appear to persist for only a few hours before collapsing, after which the virus resumes replication, but those hours may buy the cell crucial time to mount its broader antiviral response. The significance of the mechanism is underscored by human genetics: mutations in the ZNFX1 gene cause severe autoimmune and neurological disease, and the team found that some of these disease-linked mutations impair the web's formation.
The study, published in Molecular Cell under the title ZNFX1 uses two-component ubiquitin circuitry to quarantine viral RNA, was co-led by Dr Adam Fletcher in Glasgow and Professor Satpal Virdee in Dundee, with Dr Daniel Squair and PhD student Eilidh Rivers as first authors. Funding came from a UKRI Future Leaders Fellowship, the Wellcome Trust and the Medical Research Council. The work opens a new front in understanding innate immunity.