Introduction to bacteriophages

Overview of Virology

Virology is the scientific study of viruses and infectious agents characterized by a simple, acellular organization and a distinctive multiplication process. This branch of biology is particularly significant due to the role viruses play as major causes of various diseases across different organisms, including humans, animals, and plants. The COVID-19 pandemic has underscored the profound impact that viruses can have on human health, illustrating both the threat they pose and the importance of virology in public health and safety. Additionally, viruses serve as essential model organisms in molecular biology, providing insights into vital processes such as DNA replication, RNA synthesis, and protein synthesis.

Virus Existence

Viruses are unique entities that exist in two different states:

  • Extracellular: In this state, viruses are inactive and cannot reproduce outside of living cells.

  • Intracellular: Once inside a host cell, viruses commandeer the cellular machinery to synthesize their components, leading to the assembly and release of new, mature viruses (progeny).

Virus Infection

Viruses exhibit the ability to infect a wide variety of cell types, including:

  • Bacteria: These are specifically referred to as bacteriophages (or phages).

  • Eukaryotic organisms: This group includes plants, animals, protists, and fungi.

Virion Structure

General Structural Properties

A mature virus particle is known as a virion. The size of virions can range from about 20 nm in diameter to as large as a rod-shaped bacterial cell measuring 1.5 × 0.5 μm (Figure 6.1). Most virus particles require the use of electron microscopes for visualization. The most basic virions comprise a nucleocapsid, which contains:

  • Nucleic acid: This can be either DNA or RNA.

  • Capsid: This is the protein coat safeguarding the genome and facilitating transfer between host cells.

Viruses can be categorized as:

  • Enveloped viruses: These possess an outer lipid membrane.

  • Nonenveloped (or naked) viruses: These lack a membrane.

Importantly, viral structures do not contain ribosomes or cytoplasm and often lack the essential enzymes required for sustaining cellular processes.

Capsid Construction

Nonenveloped viruses build their capsid from numerous copies of one or a few minor proteins, commonly referred to as protomers. Thousands of these protomers self-assemble to create the capsid. Conversely, enveloped viruses require specific nucleocapsid proteins in addition to other proteins for membrane anchoring. For instance, the Tobacco mosaic virus (TMV) has a capsid that is composed of a single type of protomer that is 158 amino acids long and requires approximately 474 nucleotides to code, with the entire genome totaling around 6,400 nucleotides (Figure 6.3).

Types of Capsids

  • Helical Capsids: Shaped like hollow tubes with protein walls (Figure 6.1a,e). TMV serves as an archetypical example, and the size of helical capsids is influenced by both the protomers and the viral genome size.

  • Icosahedral Capsids: These are regular polyhedra featuring 20 equilateral triangular faces and 12 vertices (Figure 6.1a,e), typically constructed from capsomers composed of five or six protomers, including pentamers (pentons) and hexamers (hexons).

  • Complex Symmetry Capsids: An example includes poxviruses, large animal viruses measuring around 400 by 240 by 200 nm (Figure 6.5), which exhibit complex internal structures. Another example is T-even phages (T2, T4, T6), which have binal symmetry featuring an icosahedral head and a helical tail (Figure 6.6).

Viral Envelopes and Enzymes

The outer layer of many animal viruses is termed an envelope (Figure 6.7), formed from host cell membranes. Spike proteins, or peplomers, extend from the surface of these envelopes and play a pivotal role in mediating attachment and entry into host cells. Furthermore, several viruses carry enzymes that aid in nucleic acid replication.

Viral Genomes

Viral genomes display great diversity regarding their structure and types. Key genome types include:

  • dsDNA (double-stranded DNA)

  • ssDNA (single-stranded DNA)

  • ssRNA (single-stranded RNA)

  • dsRNA (double-stranded RNA)

Most animal viruses derive their structural properties from dsDNA, whereas plant viruses are frequently based on ssRNA. The size of viral genomes can range from as few as 4,000 nucleotides to over 2 million nucleotides, as observed in certain pandoraviruses.

Virus Life Cycle

The viral replicative cycle unfolds over five essential steps (Figure 6.9):

  1. Attachment (Adsorption): This step involves the interaction between viral ligands and host receptors.

  2. Entry into Host: The viral genome or complete nucleocapsid penetrates the cytoplasm of the host cell.

  3. Synthesis: This encompasses the production of viral nucleic acids and proteins.

  4. Assembly: Here, the formation of mature virions occurs.

  5. Release: This can transpire via mechanisms such as host cell lysis or budding.

Entry Mechanisms

Animal viruses can enter host cells through various methods:

  • Fusion: This occurs when the viral envelope merges with the host cell plasma membrane (Figure 6.10a).

  • Endocytosis: In this mechanism, the virion is internalized through endocytic pathways (Figure 6.10b).

Synthesis

The synthesis phase varies between dsDNA and RNA viruses:

  • dsDNA viruses typically mimic standard cellular transcription and translation processes.

  • RNA viruses require replication machinery that operates independently of the host cell, a topic that will be explored in greater depth in chapter 25.

Assembly and Release

The assembly of virions can be a complex process, where separate pathways may converge. The release of new virions can occur through