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Oncogenic Viruses

• Historical Background

  • Early belief that viruses cause cancer.

  • Example: Peyton Rous (1911) demonstrated that cancerous chicken tumors could be filtrated to isolate viruses that induced tumors when injected into healthy chickens.

  • Current understanding: Only a small percentage (10% to 20%) of cancers are caused by viruses.

• Types of Viral Infections

  • Persistent Viral Infections: Infections that the immune system fails to clear.

  • Subtypes:

    • Late Infections:

    • Example: Chickenpox virus remains dormant in nerve cells; can reactivate as shingles.

    • Chronic Infections:

    • Continual replication and active presence, e.g., HIV, Hepatitis C.

    • Measles can lead to subacute sclerosing panencephalitis, a fatal condition.

• Characteristics of Shingles (Reactivation of Chickenpox):

  • Occurrences: Approximately one million cases per year in the U.S.

  • Symptoms: Painful blisters, rash that is typically unilateral.

  • Risk Factors: Age (common in those over 50), immunocompromised status, extreme stress.

• Prions: Non-viral infectious agents.

  • Definition: Misfolded proteins that cause neurodegenerative diseases.

  • Notable Diseases: Creutzfeldt-Jakob disease, mad cow disease, kuru.

  • Mechanism: Abnormal prions induce normal prion proteins to misfold, leading to an accumulation of damaging proteins in the brain (spongiform changes).

• Plant Viruses:

  • Virus entry into plant cells is generally difficult due to thick cell walls.

  • Spread typically occurs via damage or insect vectors (e.g., aphids).

• Viroids:

  • Structure: Small circular pieces of RNA, lacking a protein coat; can infect plants.

  • Replication: Requires host plant cells and leads to significant agricultural disease such as potato spindle tuber disease.

• Ortho- and Metapneumoviridae:

  • Influenza Virus:

  • Type A Influenza: Causes worldwide pandemics.

  • Genome: Composed of segmented RNA (8 segments), leading to a higher mutation rate.

  • Mutation Rate: RNA-dependent RNA polymerase has a fidelity of one mistake in every 10,000 bases, compared to DNA polymerase which has one mistake in a billion.

  • Antigenic Drift and Shift:

    • Drift: Small mutations accumulate over time, leading to changes in virus surface antigens, causing seasonal flu susceptibility.

    • Shift: Occurs when different strains infect the same host cell and exchange genetic segments, leading to large mutations and potential pandemics.

Microbial Mechanisms and Pathogenicity

• Pathogenic Microorganisms

  • Not all microorganisms are capable of causing disease.

  • Virulence: The degree of harm caused by the pathogen. Can be defined as:

  • Lethality of a disease.

  • Ease of infection (e.g., flu vs. cholera).

• Portals of Entry:

  • Skin: Generally a strong barrier to pathogens; breaks (cuts/abrasions) provide entry points.

  • Mucous Membranes: Major entrance routes for pathogens due to moisture and living cells.

• Infectious Dose (ID50) and Lethal Dose (LD50):

  • ID50: The number of microorganisms required to infect 50% of a test population.

  • LD50: The number of microorganisms that would cause death in 50% of a test population.

  • Varies greatly between different pathogens depending on route of entry and host factors.

• Toxins:

  • Exotoxins: Secreted proteins that typically have a low LD50 and are sensitive to heat; examples include botulinum toxin.

  • Endotoxins: Part of the outer membrane of Gram-negative bacteria (LPS); heat-stable.

  • Toxoid: A modified toxin that has lost its ability to cause damage but can still elicit an immune response.

• AB Toxins:

  • Structure: Composed of A and B subunits.

  • B subunit: Binds to host cell receptors.

  • A subunit: Enzymatic component that exerts toxic effects after entering the cell.

Virulence Factors and Mechanisms of Adherence

• Virulence Factors: Traits enabling pathogens to cause disease.

  • Mechanisms that aid in the establishment and spread of infection.

  • Some examples include:

  • Adhesive factors: Enable bacteria to cling to host tissues (e.g., capsules, M proteins).

  • Enzymes: Excreted to dissolve surrounding tissue, aiding bacterial spread (e.g., hyaluronidase, collagenase).

• Superantigens: A special class of exotoxins that can activate a large number of T-cells, leading to an overwhelming immune response and potential shock.

• Antigenic Variation:

  • The ability of pathogens to alter their surface proteins to evade the immune response (e.g., seen in Trypanosoma brucei and Gonorrhea).

  • Mechanism of escape preventing elimination by host antibodies.

Pathogen Invasion and Iron Acquisition

• Invasion of Host Cells:

  • Some bacteria can invade host cells through ruffling, induced by invasion factors.

  • Example: Salmonella uses this strategy to infect intestinal epithelial cells.

• Iron Acquisition:

  • Critical for bacterial growth: needed for enzymes in electron transport chains.

  • Bacteria secrete siderophores that bind to host iron and facilitate bacterial uptake.

• Mechanisms of Escape from Immune Response:

  • Strategies such as secretion of IgA proteases to degrade antibodies.

Summary of Bacterial Toxins and Functions

• Exotoxins vs. Endotoxins:

  • Exotoxins: Typically produced by Gram-positive bacteria, heat-sensitive, can be neutralized by antibodies.

  • Endotoxins: Part of Gram-negative bacteria, heat-stable, non-toxic unless released in large quantities.

• Immune Evasion Strategies:

  • Pathogens may produce a range of factors to evade immune system detection and neutralization, including capsule formation, antigenic variation, and toxin production.