Genome-Scale CRISPR Screening Reveals Host Factors Required for Ribosome Formation and Viral Replication
Maikke B. Ohlson, Jennifer L. Eitson, Alexandra I. Wells, Ashwani Kumar, Seoyeon Jang, Chunyang Ni, Chao Xing, Michael Buszczak, John W. Schoggins
Abstract
Viruses are well known for their ability to co-opt host ribosomes to synthesize viral proteins. The specific factors involved in translation of viral RNAs are not fully described. In this study, we implemented a unique genome-scale CRISPR screen to identify previously uncharacterized host factors that are important for the synthesis of virally encoded protein. We found that multiple genes involved in 60S ribosome biogenesis were required for viral RNA translation. Loss of these factors severely impaired viral replication. Mechanistic studies on the AAA ATPase SPATA5 indicate that this host factor is required for a late step in ribosome formation. These findings reveal insight into the identity and function of specific ribosome biogenesis proteins that are critical for viral infections.