Viral Replication Cycles

Why This Matters

Understanding viral replication cycles is fundamental to nearly everything else you'll encounter in microbiology—from explaining why certain antibiotics don't work on viruses to predicting how pandemics spread. These cycles demonstrate core principles you're being tested on: host-pathogen interactions, molecular mechanisms of infection, genetic transfer, and the strategies pathogens use to exploit cellular machinery. When you understand the "why" behind each step, you can predict viral behavior, explain drug targets, and connect individual viruses to their broader classification.

Don't just memorize the sequence of steps—know what molecular event each stage represents and how variations in these cycles explain differences between virus types. Exam questions often ask you to compare lytic versus lysogenic cycles, explain why retroviruses are unique, or identify which stage a particular antiviral drug targets. Master the mechanisms, and you'll be ready for anything from multiple choice to complex FRQs.

---

Entry and Uncoating: Getting Inside the Host Cell

Before a virus can replicate, it must recognize, enter, and expose its genome within the host cell. These early steps determine host specificity and are prime targets for antiviral therapies.

Attachment

• Receptor-ligand binding determines host and tissue specificity—viruses can only infect cells displaying their target receptor
• Viral attachment proteins (VAPs) on the virion surface interact with specific host receptors through protein-protein or protein-carbohydrate interactions
• Host range is largely determined at this step, which is why some viruses infect only certain species or cell types

Penetration

• Entry mechanism depends on envelope status—enveloped viruses fuse with membranes, while non-enveloped viruses typically use receptor-mediated endocytosis
• Membrane fusion can occur at the plasma membrane (pH-independent) or within endosomes after acidification triggers conformational changes
• Delivery of the genome to the appropriate cellular compartment is the functional goal, setting up subsequent replication

Uncoating

• Capsid disassembly releases the viral genome into the cytoplasm or nucleus, depending on where replication occurs
• Timing varies by virus—some uncoat immediately at the plasma membrane, others require transport to specific organelles
• Uncoating signals often involve pH changes, protease activity, or interactions with cellular chaperones

---

Genome Replication and Protein Synthesis: Hijacking the Host

Once inside, viruses commandeer host machinery to copy their genomes and produce viral proteins. The replication strategy depends entirely on the type of nucleic acid the virus carries—this is the basis of the Baltimore classification system.

Replication

• Genome type dictates strategy—DNA viruses typically use host polymerases (except poxviruses), while RNA viruses must encode their own RNA-dependent RNA polymerase (RdRp)
• mRNA production is the universal requirement; all viruses must generate transcripts the host ribosome can translate
• Location matters—most DNA viruses replicate in the nucleus (accessing host replication machinery), while most RNA viruses replicate in the cytoplasm

Retroviral Replication

• Reverse transcriptase converts the ssRNA genome into dsDNA, a process unique to retroviruses and a key drug target (e.g., AZT)
• Integration via integrase inserts the viral DNA (now called a provirus) into the host chromosome, establishing permanent infection
• Proviral transcription uses host RNA polymerase II, producing both new genomic RNA and mRNA for viral proteins

---

Assembly and Release: Producing New Virions

After replication, viral components must be assembled into infectious particles and released to spread infection. The release mechanism has major implications for host cell survival and disease progression.

Assembly

• Self-assembly of capsid proteins around the viral genome occurs through spontaneous protein-protein interactions driven by thermodynamics
• Assembly location varies—many DNA viruses assemble in the nucleus, while most RNA viruses assemble in the cytoplasm
• Scaffolding proteins may assist assembly in complex viruses, then are removed or degraded in the mature virion

Release

• Lysis destroys the host cell, releasing many virions simultaneously—typical of non-enveloped viruses and bacteriophages
• Budding allows gradual release while the host cell survives temporarily, characteristic of enveloped viruses acquiring their membrane
• Release mechanism influences pathogenesis—lytic release causes acute tissue damage, while budding enables chronic, persistent infections

Enveloped Virus Budding

• Membrane acquisition occurs as viral proteins insert into host membranes (plasma membrane, ER, or Golgi) and the nucleocapsid pushes through
• Viral glycoproteins embedded in the envelope are essential for infectivity and are major targets of neutralizing antibodies
• Host cell survival during budding allows continued viral production, contributing to persistent infections and immune evasion

---

Complete Replication Cycles: Lytic vs. Lysogenic Pathways

Some viruses can switch between immediate replication and dormancy. Understanding these alternative life cycles explains phenomena like viral latency, lysogenic conversion, and reactivation diseases.

Lytic Cycle

• Immediate, productive infection proceeds through all stages (attachment → release) without interruption, producing hundreds of progeny virions
• Host cell death occurs upon release, as the cell membrane is destroyed during lysis
• Characteristic of virulent phages and many acute viral infections—rapid replication, rapid spread, rapid immune detection

Lysogenic Cycle

• Genome integration creates a prophage (in bacteria) or latent provirus (in eukaryotes) that replicates passively with host DNA
• No virion production occurs during lysogeny—the viral genome is maintained but not expressed (or minimally expressed)
• Induction triggers such as UV damage, stress, or immune suppression can reactivate the lytic cycle, explaining diseases like shingles (VZV reactivation)

---

Quick Reference Table

---

Self-Check Questions

1. Which two stages of viral replication are most affected by whether a virus is enveloped or non-enveloped, and how do the mechanisms differ?

2. A virus integrates its genome into the host chromosome and remains dormant for years before reactivating. Is this virus following a lytic cycle, lysogenic cycle, or retroviral replication—and how would you distinguish between the latter two?

3. Compare and contrast the release mechanisms of bacteriophage T4 and HIV. How does each mechanism affect the host cell, and what does this predict about disease progression?

4. An antiviral drug blocks reverse transcriptase. Which type of virus would this drug be effective against, and at which stage of replication does it act?

5. If an FRQ asks you to explain why lysogenic conversion is medically significant, which bacterial disease would serve as your best example, and what molecular event makes the bacterium pathogenic?