Viral Life Cycles

1. Introduction to Life Cycles of Viruses

Viruses are acellular and do not have the components to reproduce without the help of a host cell. To make new viruses, they must do the following:

• Find an appropriate host cell
• Attach
• Insert their genetic material
• Force the host cell’s machinery to make viral components
• Assemble new viruses
• Escape from the host cell

There are some important differences between viral replication in prokaryotic versus eukaryotic cells. This includes the location of nucleic acid replication as summarized in the table below.

Understanding viral methods of replication is important in developing ways to reduce transmission and to treat infection. Because viral replication uses the machinery of the host cell, antiviral medications need to carefully target the parts of the viral life cycle that are unique to the virus. For example, common medications used to treat HIV target enzymes involved in copying viral RNA into DNA, producing proteins, and integrating DNA into the host cell chromosome (Churchill, 2015; Scarsi, 2020). You will learn more about specific medically important viruses, prevention, and treatment in other lessons.

2. Life Cycles of Viruses With Prokaryotic Hosts

As discussed above, research into bacteriophage life cycles has been important in understanding many aspects of viral reproduction that are relevant for other types of viral infections.

Based on their life cycles, bacteriophages can be classified into two major categories: virulent and temperate phages. Infection by virulent phages typically leads to relatively rapid death of the host cell through cell lysis (bursting open of a cell resulting in cell death and release of its contents). In contrast, temperate phages can become part of the host chromosome and the viral genome is replicated as the host cell reproduces. Eventually, temperate phages can be induced to make newly assembled (progeny) viruses.

This lesson describes the lytic and lysogenic cell cycles in detail, then describes other types of viral infections.

terms to know

Virulent Phage

A phage that typically leads to the death of the host cell through cell lysis relatively quickly following infection.

Cell Lysis

Bursting of a cell.

Temperate Phage

A phage that can become part of the host chromosome, allowing it to be replicated each time the host cell reproduces. Eventually, it may be induced to begin producing new viruses.

Progeny Virus

Newly assembled viruses.

2a. The Lytic Cycle

During the lytic cycle of a virulent phage, a bacteriophage injects its genetic material into a bacterial cell and the bacterium immediately begins to produce new phages. The cycle ends when the bacterium lyses to release the progeny viruses. The five major stages of the cycle are as follows (also summarized in the image below).

step by step

1. Attachment: The phage interacts with specific bacterial surface receptors to attach to its host. Most phages have a narrow host range and may infect one species of bacteria or one strain within a species. This unique recognition can be exploited for targeted treatment of bacterial infection or for phage typing to identify unique bacterial subspecies or strains.

2. Penetration (entry): The tail sheath of the bacteriophage contracts, acting like a hypodermic needle to inject the viral genome through the outer structures of the cell (e.g., the cell wall and cell membrane) into the cytoplasm. Outer components of the phage, including the phage head, remain outside of the bacterial cell.

3. Biosynthesis: Virus-encoded enzymes that degrade the bacterial chromosome are produced. The virus then hijacks the host cell to replicate, transcribe, and translate the necessary viral components (capsomeres, sheath, base plates, tail fibers, and viral enzymes) for the assembly of new viruses. Gene expression refers to the process by which genes are used to produce proteins. The first viral genes to be expressed usually code for proteins that copy and express viral genetic material. Capsid and tail proteins are produced later.

4. Maturation: New virions are created. Phage proteins such as holin or lysozyme are used to disrupt the bacterial cell wall.

5. Lysis: The cell bursts, and progeny viruses are released into the environment to infect new cells.

terms to know

Lytic Cycle

The bacteriophage life cycle in which the viral infection rapidly leads to the production of new viruses and then lysis of the host cell (to release the viruses).

Gene Expression

The process by which genes are used to produce proteins.

2b. The Lysogenic Cycle

Lysogeny is the process by which a bacterium is infected by a temperate phage that enters the lysogenic cycle.

This cycle begins similarly to the lytic cycle. First, the phage must attach to a cell and inject its genetic material (penetration). However, the process differs once the bacteriophage genome is inside the bacterial cell. At this point, the genome can be integrated into the host cell chromosome.

After integration has occurred, the viral genome is called a prophage and the infected bacterial cell is called a lysogen.

As the bacterial cell replicates, it duplicates copies of its chromosome that contain the prophage. Therefore, it produces daughter cells that are also lysogens.

The prophage may be latent or inactive within the cell. However, the presence of the phage may alter the phenotype of the bacterium when its genes are expressed. This change in the host phenotype is called lysogenic conversion or phage conversion.

Some medically important bacteria, such as Vibrio cholerae and Clostridium botulinum, are less virulent in the absence of a specfic prophage. The prophage contains a gene that instructs the bacterial cell to produce a toxin which causes the infected bacterial cells to cause illness. As a result of phage infection, V. cholerae produces a toxin that can cause severe diarrhea, and C. botulinum produces a toxin that can cause paralysis

did you know

Cholera is the disease produced by V. cholerae infection. The phage-encoded toxin produces these symptoms. Although cholera is not a major concern in areas with good sanitation, high quality health care, and sufficient access to clean water, it causes severe illness and mortality in parts of the world that lack these resources. There are efforts underway to find better ways to reduce or even eliminate cholera infections (see D’Mello-Guyett, 2022).

Botulism can cause serious or even lethal illness. It is often transmitted through contaminated food (Lonati et al., 2020). However, the potent neurotoxin that causes these symptoms (botulinum toxin) is now used for a variety of medical purposes (see Choudhury, 2021). Among many other uses, it is used to control muscle spasms to treat migraines and to improve the appearance of facial wrinkles (Choudhury, 2021).

Under certain conditions, such as a changing environment or exposure to an antibiotic, induction can occur (Sutcliffe et al., 2021). In this process, the viral genome can be excised from the host chromosome. At this point, the temperate phage can proceed through a lytic cycle and then infect new host cells. The major stages of the cycle are as follows (also summarized in the image below).

step by step

1. Attachment
2. Penetration
3. Integration of phage genome into host chromosome as a prophage
4. Cell replication produces daughter cells containing the prophage
5. Repetition of step 4 until or unless certain conditions, such as environmental stress, occur that trigger step 6.
6. Induction (under certain conditions)
7. Biosynthesis
8. Maturation
9. Lysis

terms to know

Lysogeny

The process by which a bacterium is infected by a temperate phage that enters the lysogenic cycle.

Lysogenic Cycle

The temperate phage life cycle in which the virus genome becomes integrated with the host cell chromosome and is replicated as the host replicates. Induction may lead to excision of the viral genome and production of new viral particles followed by lysis.

Prophage

The genome of a temperate virus that has integrated into the bacterial chromosome.

Lysogen

A cell that contains a viral genome (prophage) integrated into its chromosome.

Lysogenic Conversion (Phage Conversion)

A change in the phenotype of a host cell in response to the presence of a prophage.

3. The Viral Growth Curve

Understanding the lytic life cycle is helpful in understanding the viral growth curve. This is the pattern of growth that appears when the logarithm of the number of infectious virions is plotted over time. The steps of the viral growth curve are stated below and summarized in the image below. There is a period of time during which no infectious virions (virus particles) are present, then there is a rapid increase in the number of infectious virions during the burst phase that occurs when infected cells undergo lysis.

step by step

1. Inoculation: An inoculum of virus binds to cells.
2. Eclipse: Virions penetrate the cell and are not detected in the medium.
3. Burst: Host cells release many viral particles.

Burst size refers to the number of virions released per bacterium. In contrast, viral titer is the number of virions per unit volume of solution. Unlike bacterial growth curves, viral growth curves show a sudden increase in number of viral particles associated with cell lysis. If no viable host cells remain, then the viral particles begin to degrade during the decline of the culture.

terms to know

Burst Size

Number of virions released per bacterium.

Viral Titer

Number of virions per unit volume.

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Virus Life Cycle

REFERENCES

Choudhury, S., Baker, M. R., Chatterjee, S., & Kumar, H. (2021). Botulinum Toxin: An Update on Pharmacology and Newer Products in Development. Toxins, 13(1), 58. doi.org/10.3390/toxins13010058

Churchill, D., Waters, L., Ahmed, N., Angus, B., Boffito, M., Bower, M., Dunn, D., Edwards, S., Emerson, C., Fidler, S., Fisher, M., Horne, R., Khoo, S., Leen, C., Mackie, N., Marshall, N., Monteiro, F., Nelson, M., Orkin, C., Palfreeman, A., … Winston, A. (2016). British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015. HIV medicine, 17 Suppl 4, s2–s104. doi.org/10.1111/hiv.12426

D'Mello-Guyett, L., Gallandat, K., Van den Bergh, R., Taylor, D., Bulit, G., Legros, D., Maes, P., Checchi, F., & Cumming, O. (2020). Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: A scoping review of current international guidelines. PloS one, 15(1), e0226549. doi.org/10.1371/journal.pone.0226549

Parker, N., Schneegurt, M., Thi Tu, A.-H., Lister, P., & Forster, B. (2016). Microbiology. OpenStax. Access for free at openstax.org/books/microbiology/pages/1-introduction

Scarsi, K. K., Havens, J. P., Podany, A. T., Avedissian, S. N., & Fletcher, C. V. (2020). HIV-1 Integrase Inhibitors: A Comparative Review of Efficacy and Safety. Drugs, 80(16), 1649–1676. doi.org/10.1007/s40265-020-01379-9

Sutcliffe, S. G., Shamash, M., Hynes, A. P., & Maurice, C. F. (2021). Common Oral Medications Lead to Prophage Induction in Bacterial Isolates from the Human Gut. Viruses, 13(3), 455. doi.org/10.3390/v13030455