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bioRxiv · 10.1101/2025.06.23.661133

A trove of antiviral TRIM family E3 ligases in reptiles

Boys, I. N.·Quinlan, M. R.·Elde, N. C.
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Abstract

Scaled reptiles (squamates) naturally encounter orthoflaviviruses and in some cases robustly resist infection. To identify antiviral defenses encoded in reptile genomes, we screened a green iguana cDNA library and discovered a reptilian TRIM-family E3 ubiquitin ligase that reduces dengue virus replication [~]10,000-fold in human cells. Experimental evolution identified orthoflavivirus capsid as a key determinant of harbiTRIM-mediated restriction, revealing a convergence of TRIMs on viral capsids as targets during viral infections. HarbingerTRIM is situated near an endogenized Harbinger transposon in various copy numbers in squamate genomes. Analysis of a sampling of reptile harbiTRIM variants revealed distinct antiviral properties, highlighting the immune diversity present in non-mammal animal genomes as a largely untapped reservoir of antiviral defenses.

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Boys, I. N., Quinlan, M. R., Elde, N. C.. 2025-06-25. A trove of antiviral TRIM family E3 ligases in reptiles. https://doi.org/10.1101/2025.06.23.661133

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