Cryo-EM reveals infection steps of single-stranded RNA bacteriophages

Single-stranded RNA bacteriophages (ssRNA phages) are small spherical RNA viruses that infect bacteria with retractile pili. The single positive-sense genomic RNA of ssRNA phages, which is protected by a capsid shell, is delivered into the host via the retraction of the host pili. Structures involved in ssRNA phage infection cycle are essential for understanding the underlying mechanisms that can be used to engineer them for therapeutic applications. This review summarizes the recent breakthroughs in high-resolution structural studies of two ssRNA phages, MS2 and Qβ, and their interaction with the host, E. coli, by cryo-electron microscopy (cryo-EM). These studies revealed new cryo-EM structures, which provide insights into how MS2 and Qβ package the RNA, lyse E. coli, and adsorb to the receptor F-pili, responsible for conjugation. Methodologies described here can be expanded to study other ssRNA phages that target pathogenic bacteria.