Bacteriophage T4

Abstract

Bacteriophage T4 and its host bacterium, Escherichia coli, can be considered among the earliest model organisms – biological systems that attract large numbers of investigators who, because of technical or conceptual advantages of the system, use the system to investigate processes and mechanisms of general significance in biology. Beginning in the mid-twentieth century, studies focused on bacteriophage T4 revealed essential features of the molecular nature of genes and genomes, mechanism and fidelity of DNA replication, genetic recombination, DNA repair, control of gene expression, genome organisation, assembly of complex macromolecular structures and pre-emption of cell metabolism by virus infection. Although much of the molecular biology research community has moved on to eukaryotic model organisms, such as yeast, nematode worms, fruitflies, the plant Arabidopsis, zebrafish and mice, bacteriophage T4 still presents the best opportunities for understanding at the molecular level DNA replication and recombination, and macromolecular assembly. In addition, T4 and related phages are being used in investigations of bacteriophage therapy. Finally, recent analyses of DNA packaging and morphogenesis have suggested applications of T4 as a gene delivery vehicle.

Key Concepts

• Bacteriophage T4 presents numerous technical advantages as a model for studying virus reproduction or gene organisation and expression.
• Bacteriophage T4 is representative of a large group of closely related phages found in varied environments worldwide.
• Bacteriophage T4 is a virulent phage, which always lyses and kills its host bacterium.
• The T4 virion has a complex multiprotein structure with a contractile tail that serves both for adsorption to host cells and for intracellular delivery of the viral genome.
• Bacteriophage T4 contains a large, linear double-stranded DNA genome, with chemical modifications of its cytosine residues.
• The T4 genome is circularly permuted and terminally redundant with respect to base sequence; these features protect against information loss during replication of a linear DNA.
• The T4 genome encodes numerous enzymes, used to support replication of the viral genome and to synthesise deoxyribonucleotides to support the enormous rate of DNA accumulation in infected cells.
• T4 uses host cell RNA polymerase for transcription of its own genes, but it modifies the bacterial enzyme, both to prevent its transcription of bacterial genes after infection and to contribute towards a timed viral gene transcription program.
• T4 morphogenesis involves separate subassembly pathways for viral heads, tails, tail baseplates and fibres, with the substructures assembling spontaneously.