🦠Virology Unit 4 – Virus Replication Cycles – Lytic and Lysogenic

Key Concepts

• Viruses are obligate intracellular parasites that require host cells to replicate
• Two main types of viral replication cycles: lytic and lysogenic
• Lytic cycle involves direct replication and lysis of the host cell
  • Viruses hijack host cell machinery to produce new virions
  • Newly assembled viruses are released through cell lysis (rupture)
• Lysogenic cycle incorporates viral genome into the host cell's DNA
  • Viral DNA is replicated along with the host cell's genome
  • Viral genes may remain dormant (prophage) until triggered to enter the lytic cycle
• Stages of viral replication: attachment, penetration, uncoating, replication, assembly, and release
• Host cell interactions play a crucial role in determining the outcome of viral infection
  • Cell surface receptors facilitate viral attachment and entry
  • Immune response can limit viral replication and spread

Virus Structure Basics

• Viruses consist of genetic material (DNA or RNA) encased in a protein coat (capsid)
• Some viruses have an additional lipid envelope surrounding the capsid
• Capsids can be icosahedral (polyhedral with 20 faces), helical, or complex in shape
• Viral genomes can be single-stranded or double-stranded, linear or circular
• Viruses encode essential proteins for replication and host cell manipulation
  • Enzymes (polymerases, integrases) facilitate viral genome replication and integration
  • Structural proteins form the capsid and ensure proper assembly
• Virus size ranges from ~20 nm (parvoviruses) to ~400 nm (poxviruses)
• Lack of cellular organelles and inability to replicate independently define viruses as non-living entities

Lytic Cycle Overview

• Lytic cycle is a destructive process that leads to the death of the infected host cell
• Stages: attachment, penetration, uncoating, replication, assembly, and release
• Attachment: viruses bind to specific receptors on the host cell surface
• Penetration: viruses enter the cell through endocytosis or membrane fusion
• Uncoating: viral genome is released into the host cell cytoplasm
• Replication: viral genes are expressed, and the genome is replicated using host cell machinery
  • Viral proteins are synthesized using host cell ribosomes
  • Genome replication occurs in the nucleus (DNA viruses) or cytoplasm (RNA viruses)
• Assembly: new virions are assembled from replicated components
• Release: newly formed viruses are released through cell lysis, causing host cell death
• Examples of viruses that undergo lytic cycle: influenza virus, poliovirus, and rhinovirus (common cold)

Lysogenic Cycle Overview

• Lysogenic cycle allows the virus to establish a latent infection without immediately killing the host cell
• Viral genome integrates into the host cell's DNA as a prophage
• Prophage is replicated along with the host cell's genome during cell division
  • Viral genes are passed on to daughter cells
  • Prophage can remain dormant for extended periods (latency)
• Induction: environmental factors or cellular signals can trigger the prophage to enter the lytic cycle
  • Stressors (UV radiation, chemicals) or immune suppression can lead to induction
  • Prophage excises from the host genome and initiates lytic replication
• Lysogenic cycle allows viruses to maintain a reservoir of genetic material within host cells
• Examples of viruses that undergo lysogenic cycle: lambda phage, herpes simplex virus (HSV), and human immunodeficiency virus (HIV)

Stages of Viral Replication

1. Attachment: virus binds to specific receptors on the host cell surface
   • Receptor specificity determines host range and tissue tropism
   • Viral surface proteins (spikes, fibers) facilitate attachment
2. Penetration: virus enters the host cell through endocytosis or membrane fusion
   • Enveloped viruses fuse their envelope with the host cell membrane
   • Non-enveloped viruses are engulfed by the cell membrane (endocytosis)
3. Uncoating: viral capsid is degraded, releasing the viral genome into the cytoplasm
   • Host cell enzymes or viral proteins may assist in uncoating
4. Replication: viral genome is replicated, and viral proteins are synthesized
   • DNA viruses typically replicate in the nucleus using host cell polymerases
   • RNA viruses replicate in the cytoplasm using viral RNA-dependent RNA polymerases
   • Viral genes are expressed in a regulated manner (early and late genes)
5. Assembly: new virions are assembled from replicated components
   • Capsid proteins self-assemble around the viral genome
   • Enveloped viruses acquire their envelope from host cell membranes
6. Release: newly formed viruses are released from the host cell
   • Lytic cycle: viruses are released through cell lysis
   • Lysogenic cycle: viruses can be released without immediate cell death
   • Some viruses (influenza) use budding to exit the cell without lysis

Comparison: Lytic vs Lysogenic

• Lytic cycle:
  • Direct replication and lysis of the host cell
  • Rapid production of new virions
  • Host cell is destroyed in the process
  • Examples: influenza virus, poliovirus
• Lysogenic cycle:
  • Integration of viral genome into the host cell's DNA (prophage)
  • Viral genes are replicated along with the host genome
  • Latent infection without immediate cell death
  • Prophage can be induced to enter the lytic cycle
  • Examples: lambda phage, herpes simplex virus (HSV)
• Both cycles involve attachment, penetration, uncoating, replication, assembly, and release
• Lytic cycle is faster and more destructive, while lysogenic cycle allows for long-term survival of the virus
• Some viruses (HIV) can undergo both lytic and lysogenic cycles depending on the host cell type and conditions

Host Cell Interactions

• Viruses rely on host cell machinery for replication and survival
• Attachment: viral surface proteins interact with specific host cell receptors
  • Receptor specificity determines host range and tissue tropism
  • Examples: influenza virus hemagglutinin binds to sialic acid receptors on respiratory cells
• Entry: viruses exploit host cell endocytic pathways or membrane fusion mechanisms
  • Clathrin-mediated endocytosis is a common entry route for many viruses
  • Enveloped viruses (HIV) fuse their envelope with the host cell membrane
• Intracellular transport: viruses use host cell cytoskeleton for movement within the cell
  • Microtubules and motor proteins (dynein, kinesin) facilitate viral transport to replication sites
• Immune evasion: viruses employ various strategies to evade host immune responses
  • Antigenic drift and shift (influenza) allow viruses to escape antibody recognition
  • Viral proteins can interfere with antiviral signaling pathways (interferon response)
• Cell cycle modulation: some viruses manipulate the host cell cycle to create favorable conditions for replication
  • DNA viruses (adenovirus) can induce S phase to promote viral genome replication
• Apoptosis: viruses can induce or inhibit programmed cell death to facilitate spread or persistence
  • Lytic viruses (influenza) may induce apoptosis to promote release of new virions
  • Latent viruses (EBV) may inhibit apoptosis to maintain long-term infection

Real-World Applications

• Vaccine development: understanding viral replication cycles is crucial for designing effective vaccines
  • Live attenuated vaccines (measles, mumps) contain weakened viruses that can replicate without causing disease
  • Inactivated vaccines (polio) use killed viruses that cannot replicate but still elicit an immune response
• Antiviral drug design: targeting specific stages of the viral replication cycle
  • Entry inhibitors (enfuvirtide) prevent HIV from fusing with host cell membrane
  • Protease inhibitors (ritonavir) block viral protein maturation and assembly
  • Reverse transcriptase inhibitors (zidovudine) inhibit HIV genome replication
• Gene therapy: using viruses as vectors to deliver therapeutic genes into cells
  • Retroviruses (lentivirus) can integrate genes into the host cell genome for long-term expression
  • Adenoviruses can deliver genes for transient expression without genome integration
• Oncolytic virotherapy: using viruses that selectively replicate in and kill cancer cells
  • Genetically modified viruses (adenovirus, herpes simplex virus) can target and destroy tumor cells while sparing normal tissue
  • Viral replication within tumors can stimulate anti-tumor immune responses
• Bacteriophage therapy: using viruses that infect and kill bacteria as an alternative to antibiotics
  • Phages can be used to treat antibiotic-resistant bacterial infections
  • Lytic phages (T4) can rapidly kill bacteria without affecting human cells