Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense

Fernbach, Sonja; Spieler, Eva E; Busnadiego, Idoia; Karakus, Umut; Lkharrazi, Anouk; Stertz, Silke; Hale, Benjamin G

doi:10.1016/j.celrep.2022.110549

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Fernbach, S., Spieler, E. E., Busnadiego, I., Karakus, U., Lkharrazi, A., Stertz, S., & Hale, B. G. (2022). Restriction factor screening identifies RABGAP1L-mediated disruption of endocytosis as a host antiviral defense. Cell Reports, 38(12), 110549. https://doi.org/10.1016/j.celrep.2022.110549

Abstract

Host interferons (IFNs) powerfully restrict viruses through the action of several hundred IFN-stimulated gene (ISG) products, many of which remain uncharacterized. Here, using RNAi screening, we identify several ISG restriction factors with previously undescribed contributions to IFN-mediated defense. Notably, RABGAP1L, a Tre2/Bub2/Cdc16 (TBC)-domain-containing protein involved in regulation of small membrane-bound GTPases, robustly potentiates IFN action against influenza A viruses (IAVs). Functional studies reveal that the catalytic