Here in Austria, as in many other places, it’s been a hot end to another unusually warm month (this year, only May has been cooler than average). Blistering heatwaves like the one expected to peak in Europe this week are just one consequence of climate change. Another is the spread of vector-borne diseases, as mosquitoes and other vectors expand into new regions. For example, mosquito-borne flaviviruses causing diseases like dengue fever, Zika, and West Nile fever already infect over 400 million people a year and are set to continue spreading to temperate regions. There are currently no effective antiviral drugs for flaviviruses.
Unlike mammals and birds, some scaled reptiles are resistant to flavivirus infection, but the mechanisms underlying this resistance are unknown. A recent preprint reported a screen for viral resistance genes in iguanas, identifying a TRIM-family E3 ubiquitin ligase that reduces dengue virus replication in human cells ~10,000-fold. The authors provide evidence that the E3 ligase targets the viral capsid protein for degradation, a strategy distinct from known anti-flavivirus strategies. Crucially, flaviviruses depend on (non-degradative) capsid ubiquitylation for infection, so it might be difficult for them to evolve TRIM resistance without losing infectivity. Indeed, the authors used experimental evolution to show how flaviviruses might be forced into an evolutionary corner: TRIM resistance (enabled by mutations in ubiquitin-modifiable capsid residues) came at the cost of reduced fitness in human cells.
Finally, the authors identified a whole family of similar genes in reptiles with varied antiviral activity, “highlighting the vast potential of querying diverse animal genomes for discovering new defenses to pandemic viruses.”
A trove of antiviral TRIM family E3 ligases in reptiles
In bioRxiv, 25 June 2025
From the group of Nels Elde, University of Utah and Howard Hughes Medical Institute
Snippet by Katrina Woolcock.
Image credit: Figure 1 from Boys et al. cited above (CC-BY-NC 4.0).
