A trove of antiviral TRIM family E3 ligases in reptiles

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.