Lecture on Viral Replication and Pathogenesis

Multiplication Cycle of Viruses

  • Misnomer of Lifecycle

    • Commonly referred to as the lifecycle of a virus, however, viruses are not considered living organisms.

Phases of the Replication Cycle

  • Absorption & Attachment

    • The virus must absorb to the host cell.

    • It uses a specific receptor on the host cell for attachment.

    • Example: Spike protein of COVID-19 recognizes a receptor on the cell surface.

    • Comparison to the:lock and key model:

    • The virus is the key fitting into the lock of the host cell receptor.

  • Penetration & Uncoating

    • Once attached, the virus penetrates the cell membrane.

    • The mechanism of uncoating can vary:

    • Direct entry entails membranes fusing, allowing the viral contents to enter.

    • Vesicular entry: the virus may enter in a vacuole that subsequently undergoes digestion, freeing the viral nucleic acid.

  • Synthesis

    • The viral DNA or RNA must be synthesized to produce proteins.

    • Types of nucleic acids:

      • Double-stranded RNA

      • Single-stranded RNA

      • Double-stranded DNA

      • Single-stranded DNA

    • The nucleic acid's type influences how the proteins are synthesized and how the genome is replicated.

  • Assembly Stage

    • Proteins that comprise the capsid are synthesized, often in the cytoplasm or nucleus.

    • The genome is replicated and organized into a capsid:

    • Capsid self-assembles.

    • The nucleic acid binds to the capsid, forming a nucleocapsid structure.

    • Spike proteins are inserted into the host cell membrane for future viral particles when they bud off.

Release of New Viruses

  • Types of Viruses & Release Mechanisms:

    • Non-enveloped viruses:

    • Released via cell lysis, rupturing the cell.

    • Enveloped viruses:

    • Released through exocytosis, budding off from the cell membrane.

      • Example: COVID-19 and HIV can exit this way.

      • Importance:

      • For flu viruses, viral proteins on the host membrane can be cleaved by an enzyme leading to release; Tamiflu inhibits this cleaving step.

  • Number of Released Virions:

    • The quantity of viruses released varies based on:

    • Virus type.

    • Health of the host cell.

    • Example Data:

      • Poxvirus can release 3,000 to 4,000 virions.

      • Polio virus can release up to 100,000 virions.

      • Consideration of cumulative impact of many infected cells.

Cytopathic Effects from Viral Infection

  • Definition of Cytopathic Effects:

    • Visible damage to host cells that can be observed microscopically.

    • Includes:

    • Changes in shape or size of cells

    • Presence of intracellular elements not typically found in healthy cells.

      • Examples include: Inclusion bodies (masses of viruses or damaged organelles) or syncytia (fusion of several infected cells into larger multi-nucleated cells).

Long-Term Presence of Viruses

  • Proviruses and Chronic Infections:

    • Some viruses integrate into the host genome or remain dormant:

    • Provirus: Viral DNA integrated into host DNA (Example: HIV).

    • Latent infections: Viruses that can reactivate later in life (e.g., Chickenpox -> Shingles).

Oncoviruses and Cancer

  • Oncoviruses:

    • About 20% of cancers are linked to oncoviruses.

    • Mechanisms of cancer transformation include:

    • Integration of viral oncogenes that promote uncontrolled cell growth.

    • Non-integrating viruses altering gene expression leading to malignancy.

    • Examples of oncogenic viruses:

    • Human Papillomavirus (HPV), Hepatitis B.

Bacteriophages: Viral Infections of Bacteria

  • Definition:

    • Bacteriophages are viruses that infect bacteria.

  • Two Replication Cycles:

    • Lytic Cycle:

    • Attachment, penetration, and immediate injection of DNA into bacteria, leading to cell lysis releasing new phages.

    • Lysogenic Cycle:

    • Infection leading to integration of viral DNA into bacterial DNA, replicated during bacterial division without immediate harm.

      • Induction of lytic cycle when conditions trigger viral activation.

Mechanisms of Viral Pathogenicity

  • Transduction:

    • Process where bacteriophages can transfer genetic material between bacterial cells, promoting virulence.

  • Examples of Bacteria and Associated Toxins:

    • Corynebacterium diphtheriae (diphtheria toxin).

    • Vibrio cholerae (cholera toxin).

    • Clostridium botulinum (botulinum toxin).

Treatment of Viral Infections

  • Challenges with Antibiotics:

    • Antibiotics target bacteria, not viruses.

  • Selective Toxicity Challenge:

    • Viruses depend on host cells for replication, making it difficult to target without impacting host cells directly.

    • Example treatment strategies for HIV focus on targeting unique features of its lifecycle (e.g., reverse transcriptase, integrase inhibitors).

Vaccines Against Viral Infections

  • Vaccine Development Variability:

    • The success of vaccine development varies due to virus behavior and replication mechanisms:

    • DNA viruses generally accumulate mutations slower than RNA viruses, making vaccines easier to develop for the former.

    • For example, polio vaccine development was highly successful compared to HIV.

Other Infectious Agents

  • Prions:

    • Infectious proteins causing neurodegenerative diseases (e.g., Creutzfeldt-Jakob, Mad Cow Disease).

    • They cause abnormal protein folding and aggregation leading to neurodegeneration.

  • Satellites and Viroids:

    • Satellite viruses: Require helper viruses for infection.

    • Viroids: Consist of short, circular RNA molecules, infecting plants with economic implications for agriculture.