Half a Century of Research on Membrane-Containing Bacteriophages: Bringing New Concepts to Modern Virology

Abstract

Half a century of research on membrane-containing phages has had a major impact on virology, providing new insights into virus diversity, evolution and ecological importance. The recent revolutionary technical advances in imaging, sequencing and lipid analysis have significantly boosted the depth and volume of knowledge on these viruses. This has resulted in new concepts of virus assembly, understanding of virion stability and dynamics, and the description of novel processes for viral genome packaging and membrane-driven genome delivery to the host. The detailed analyses of such processes have given novel insights into DNA transport across the protein-rich lipid bilayer and the transformation of spherical membrane structures into tubular nanotubes, resulting in the description of unexpectedly dynamic functions of the membrane structures. Membrane-containing phages have provided a framework for understanding virus evolution. The original observation on membrane-containing bacteriophage PRD1 and human pathogenic adenovirus has been fundamental in delineating the concept of "viral lineages", postulating that the fold of the major capsid protein can be used as an evolutionary fingerprint to trace long-distance evolutionary relationships that are unrecognizable from the primary sequences. This has brought the early evolutionary paths of certain eukaryotic, bacterial, and archaeal viruses together, and potentially enables the reorganization of the nearly immeasurable virus population (~1 × 10³¹) on Earth into a reasonably low number of groups representing different architectural principles. In addition, the research on membrane-containing phages can support the development of novel tools and strategies for human therapy and crop protection.

Keywords: Corticoviridae; Cystoviridae; Plasmaviridae; Tectiviridae; lipid-containing bacteriophage; virus evolution; virus–host interaction.

Figure 1

Entry mechanisms of membrane-containing phages. (a) Pseudomonas phage phi6. Phi6 attaches to a type IV pilus, which retracts and brings the virion into contact with the bacterial outer membrane. The viral membrane (envelope) fuses with the host outer membrane, releasing the nucleocapsid into periplasmic space. The peptidoglycan layer is digested by a virally-encoded lytic enzyme, after which the nucleocapsid enters the cytoplasm via an endocytic-like route. Finally, the nucleocapsid shell dissociates, releasing the phi6 virion core (polymerase complex). (b) Pseudomonas phage PRD1. Upon attachment to the host receptor, the internal membrane vesicle of phage PRD1 transforms into a proteo-lipidic tube, which traverses the cell envelope and provides a conduit for transferring the linear dsDNA genome into the cytoplasm. (c) Pseudoalteromonas phage PM2. It has been suggested that after phage PM2 binds to the host receptor, its protein capsid dissociates triggering the fusion between the internal membrane vesicle and the bacterial outer membrane and consequently the release of the circular dsDNA genome into the cell. CM, cytoplasmic membrane; PG, peptidoglycan layer; OM, outer membrane of the envelope in Gram-negative host bacterium.