Viral Replication Cycles: Lytic, Lysogenic, and Beyond

1) General Replication Stages (A Host-Dependent Process)

Viruses do not replicate by themselves; they are replicated by host cells after a successful infection. Despite the diversity of viruses, many follow a recognizable sequence of stages. The details differ by virus type and host, but the logic is consistent: get the genome into a suitable cell, use host resources to make viral parts, then release new virions.

Stage A — Attachment (Adsorption)

Goal: Bind to specific molecules on the host surface (receptors). This step largely determines which cells can be infected.

• What happens: Viral surface proteins (or phage tail fibers) bind host receptors with a “lock-and-key” fit.
• Practical implication: If a receptor is absent or altered, attachment fails and infection is blocked.

Stage B — Entry (Penetration)

Goal: Deliver the viral genome (or sometimes the entire capsid) into the host.

• Bacteriophages: Often inject the genome through the cell envelope while the capsid remains outside.
• Animal viruses: Often enter by membrane fusion or endocytosis (covered later in this chapter).

Stage C — Uncoating

Goal: Remove the capsid (and any envelopes) so the genome becomes accessible for replication and gene expression.

• Where it happens: In the cytoplasm, in endosomes, or at the nuclear pore—depending on the virus.
• Why it matters: Uncoating is a vulnerable step; if it is blocked, replication cannot proceed.

Stage D — Genome Replication

Goal: Make copies of the viral genome using host enzymes, viral enzymes, or both.

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• Key idea: The host cell provides nucleotides, energy, ribosomes, and often polymerases; many viruses also bring or encode their own polymerases.
• Checkpoint: The virus must replicate its genome in the correct cellular location (nucleus or cytoplasm) and in the correct form (DNA or RNA intermediates).

Stage E — Protein Synthesis (Gene Expression)

Goal: Produce viral proteins (capsid proteins, enzymes, and proteins that modify host processes).

• Host dependence: Translation is performed by host ribosomes.
• Timing: Many viruses make “early” proteins (often replication-related) and “late” proteins (often structural components).

Stage F — Assembly (Maturation)

Goal: Put genomes and structural proteins together into new virions.

• Self-assembly: Many capsids assemble spontaneously when components reach sufficient concentration.
• Quality control: Some viruses require specific packaging signals so the correct genome is loaded.

Stage G — Release

Goal: Exit the host cell to spread to new cells.

• Lysis: The cell breaks open, releasing many virions at once (common for many phages and some animal viruses).
• Budding/exocytosis: Virions exit wrapped in host-derived membrane (common for many enveloped animal viruses).

2) Bacteriophage Lytic Cycle (Baseline Model)

The lytic cycle is a clear, step-by-step example of viral replication that ends with host cell lysis and release of progeny phage. Use it as a baseline to compare other strategies.

Step-by-step lytic cycle

1. Attachment: Phage tail fibers bind specific receptors on the bacterial surface.
2. Entry: The phage injects its genome into the cytoplasm; the capsid typically remains outside.
3. Early gene expression: Viral genes redirect host processes (for example, prioritizing viral nucleic acid synthesis).
4. Genome replication: Multiple copies of the phage genome are produced.
5. Late gene expression: Structural proteins (capsid, tail) and lysis proteins are synthesized.
6. Assembly: Heads and tails assemble; genomes are packaged into capsids.
7. Release (lysis): Phage-encoded proteins disrupt the bacterial envelope; the cell ruptures and releases new phage.

Labeled flow diagram (lytic cycle)

[1] Attachment (receptor binding on bacterium surface)  ──►  [2] Genome entry (injection)  ──►  [3] Early genes (host takeover)  ──►  [4] Genome replication  ──►  [5] Late genes (capsid/tail + lysis proteins)  ──►  [6] Assembly + genome packaging  ──►  [7] Lysis + release (burst)

Practical example: mapping a lab observation to a stage

If a bacterial culture suddenly clears (becomes less turbid) after phage addition, that visual change is consistent with Stage 7: lysis. If phage are present but the culture does not clear, possible explanations include failure at attachment (no receptor) or at entry (injection blocked), or a non-lytic strategy such as lysogeny.

3) Lysogeny and Prophages: Integration, Dormancy, Induction, and Trait Changes

Some bacteriophages can follow an alternative path: instead of immediately producing progeny and lysing the cell, they establish a stable relationship where the viral genome persists inside the bacterium. In this state, the viral genome is called a prophage, and the bacterium is a lysogen.

How lysogeny works (step-by-step)

1. Attachment and entry: As in the lytic cycle, the phage binds and delivers its genome.
2. Decision point: Viral regulatory proteins bias the outcome toward lytic growth or lysogeny based on conditions (for example, host stress level and resource availability).
3. Integration or stable maintenance: The phage genome becomes part of the bacterial chromosome (integration) or persists as a stable element in the cell.
4. Dormancy with replication: When the bacterium divides, the prophage is copied along with the host DNA, passing to daughter cells.
5. Repression of lytic genes: A phage-encoded repressor keeps lytic functions “off,” maintaining dormancy.

Induction: switching from lysogenic to lytic

Induction is the process where a prophage exits dormancy and enters the lytic cycle. Common triggers include:

• DNA damage responses: For example, UV exposure or chemicals that damage DNA can activate bacterial stress pathways that inactivate the prophage repressor.
• Severe stress: Conditions that threaten host survival can favor prophage escape via lytic replication.

After induction, the sequence typically proceeds through genome replication, protein synthesis, assembly, and lysis.

Consequences for bacterial traits (including toxin genes)

A prophage can change bacterial traits by bringing in new genes or altering gene regulation. This is sometimes called lysogenic conversion. Importantly, not all prophages carry “extra” genes, and not all trait changes are harmful; the effects depend on the specific genes involved.

Cautious beginner-friendly example (conceptual): Imagine a bacterium that normally produces no toxin. A temperate phage infects it and becomes a prophage. If that prophage happens to carry a toxin gene (or a regulator that increases toxin expression), the lysogen may now produce a toxin. This does not mean “phages create toxins in general”; it means some specific phages can carry specific genes that alter host phenotype. In real settings, this matters because induction (for example, after DNA damage) can both increase phage production and, in some cases, change expression of prophage-encoded factors.

4) Animal Virus Strategies: Entry, Replication Location, and Release

Animal viruses face different barriers than phages: they must cross a plasma membrane, may encounter endosomes, and often must navigate to specific cellular compartments. The same general stages apply, but the “how” differs.

Entry differences: fusion vs endocytosis

• Fusion (common for enveloped viruses): Viral envelope merges with the host plasma membrane (or an endosomal membrane), delivering the nucleocapsid into the cytoplasm. Fusion requires specific viral proteins and appropriate host receptors.
• Endocytosis: The host cell engulfs the virus into an endosome. The virus then escapes by fusion with the endosomal membrane or by disrupting the endosome, followed by uncoating.

Step-by-step comparison:

• Fusion route: attachment → membrane fusion → nucleocapsid release → uncoating
• Endocytosis route: attachment → endocytosis → endosomal acidification/trigger → escape to cytoplasm → uncoating

Replication location: nucleus vs cytoplasm

Where genome replication and transcription occur depends on the virus and its enzymes.

• Nuclear replication (often DNA viruses): The virus delivers its genome to the nucleus to use host nuclear enzymes and access nuclear processes. This requires trafficking to the nucleus and often passage through nuclear pores.
• Cytoplasmic replication (many RNA viruses): The virus replicates in the cytoplasm, frequently forming replication complexes on intracellular membranes. These viruses typically encode polymerases needed for RNA genome replication.

Practical cue: If a virus must enter the nucleus, then blocking nuclear import can block infection even after entry and uncoating.

Release strategies: budding vs lysis

• Budding (common for enveloped viruses): Viral proteins accumulate in a host membrane (plasma membrane or internal membranes). The nucleocapsid buds out, acquiring an envelope. Budding may allow prolonged production without immediate cell death, though it can still damage the cell.
• Lysis (common for many non-enveloped viruses): The cell ruptures, releasing virions. This is often abrupt and destructive.

Practical example: If microscopy shows viral proteins concentrated at the cell membrane and virions appearing at the surface, that pattern fits assembly and budding. If instead cells swell and rupture with sudden release, that fits lysis.

5) Error Rates and Variation in RNA Viruses: Rapid Change

Many RNA viruses replicate with polymerases that lack robust proofreading. As a result, copying errors occur more frequently than in many DNA-based replication systems. These errors create a diverse population of related genomes.

Why higher error rates matter

• Variation: Each replication round can generate mutants.
• Selection: In a new environment (new host immunity, new tissue, antiviral drug), variants that replicate better under those conditions can become more common.
• Trade-off: Too many errors can be harmful because essential genes may be damaged; successful viruses balance adaptability with maintaining function.

Practical way to think about it

Imagine a large population of virions produced during infection. If even a small fraction carry mutations, some may partially evade an antibody or resist a drug that targets a specific viral enzyme. This does not guarantee escape, but it increases the chances that a suitable variant exists when selection pressure appears.

Scenario Analysis: Identify Which Stage a Drug or Immune Factor Could Block

For each scenario below, identify the most likely replication stage being blocked (attachment, entry, uncoating, genome replication, protein synthesis, assembly, release). Then check the provided mapping.

Scenarios

1. Neutralizing antibodies bind a viral surface protein and prevent the virus from binding host receptors.
2. A small molecule prevents an enveloped virus from fusing with the host membrane after receptor binding.
3. A drug raises endosomal pH so the virus cannot undergo the pH-triggered change needed to escape the endosome.
4. A polymerase inhibitor prevents copying of the viral genome.
5. A compound blocks a viral protease needed to process viral polyproteins into functional proteins.
6. A mutation in a bacterial receptor prevents phage binding; phage are present but no infection occurs.
7. A drug prevents formation of the viral capsid, leading to many viral proteins but few infectious particles.
8. An inhibitor blocks a viral neuraminidase-like release function (conceptually: virions form but remain stuck to the cell surface).
9. UV light damages bacterial DNA and activates stress responses, followed by sudden phage production and bacterial lysis in a lysogen.

Answer key (stage mapping)