Antiviral function and viral antagonism of the rapidly evolving dynein activating adaptor NINL

• DOI: 10.7554/elife.81606
• Publication Date: 2022-10-12T10:15:49Z
• Authors: Donté Alexander S...; Christopher Beier...; Swetha Mahesula; Miles R Corley; John Salogiannis; Brian V Tsu; Bryant Cao; Andrew P Ryan; Hiroyuki Hakozawki; Samara L Reck-Pet...; Matthew D Daugherty
• Keywords: Intrinsic immunity

Viruses interact with the intracellular transport machinery to promote viral replication. Such host–virus interactions can drive host gene adaptation, leaving signatures of pathogen-driven evolution in genomes. Here, we leverage these genetic identify dynein activating adaptor, ninein-like (NINL), as a critical component antiviral innate immune response and target antagonism. Unique among genes encoding components active complexes, NINL has evolved under recurrent positive (diversifying) selection, particularly its carboxy-terminal cargo-binding region. Consistent role for immunity, demonstrate that knockout cells exhibit an impaired interferon, resulting increased permissiveness Moreover, show proteases encoded by diverse picornaviruses coronaviruses cleave disrupt function host- virus-specific manner. Our work reveals importance utility using conflicts uncover new immunity targets