Viruses & Prions

6.1: General Virus Characteristics

  • Viruses are Nonliving Pathogens

    • Definition: Viruses are submicroscopic, infectious agents that are acellular and obligate intracellular pathogens.

    • Size: Extremely small in size, typically ranging from 20–400 nm.

    • Virology: The scientific study of viruses and viral diseases.

  • Viruses Exhibit Diverse Structural and Genomic Features

    • Infectivity: Viruses can infect every living organism on the planet.

    • Focus on:

    • Bacteriophages (or phages) — viruses that infect bacteria.

    • Animal viruses — viruses that infect animals and humans.

  • Virion

    • A virion is defined as a single, infectious virus particle.

    • Contains an exterior protective protein capsid.

    • Composed of genetic material, which can be either DNA or RNA.

Viral Capsids

  • Capsid

    • The capsid is a protein shell that packages and protects the viral genome.

    • Made of smaller units called capsomeres.

    • Most animal viruses exhibit either helical or icosahedral capsids.

    • Deviations from these structures are classified as complex capsids.

    • Example: Bacteriophages show a complex capsid structure, featuring additional complex structures to inject their genome into target cells.

Viral Envelopes

  • Enveloped viruses are characterized by having a lipid-based envelope that surrounds the capsid.

    • Arises from the virus budding off the host cell, taking a portion of the host cell's membrane with them.

    • Naked (or nonenveloped) viruses lack an envelope, which results from the lysis (bursting) of the host cell.

    • Animal viruses can be either enveloped or naked, while bacteriophages are always naked since they lyse host cells.

Viral Spikes (Peplomers)

  • Definition: Spikes (or peplomers) protrude from either the viral capsid or envelope and are glycoprotein extensions that assist in virus attachment and entry into host cells.

    • These spikes contribute to host range and tissue tropism, binding only to specific factors on a given host cell.

    • Example: Influenza viruses frequently mutate and undergo minor changes in spike proteins.

    • Specific spikes associated with Influenza A include:

    • Hemagglutinin (HA)

    • Neuraminidase (NA)

Viral Genomes

  • Most viruses possess fewer than 300 genes.

    • Viral genes encode:

    • Capsomere proteins

    • Enzymes required for viral replication

    • Various structural factors

    • Viral genomes can be classified as:

    • Either RNA or DNA

    • Single-stranded or double-stranded

    • Single or segmented sections

    • Circular or linear

    • The primary goal of all viruses is to compel a host cell to produce viral proteins, thereby enabling the construction of more virions.

Viral Genomes Change Over Time

  • Viruses mutate at a faster rate compared to living infectious agents due to:

    • Rapid replication time

    • Large quantities of virions produced

Reassortment Events & Random Mutations

  • Reassortment can occur when two distinct viral strains co-infect a single host cell, leading to new viral strains.

  • RNA genomes tend to mutate more frequently than DNA because:

    • DNA polymerases possess proofreading capabilities while RNA polymerases do not.

    • Mutations can have various effects:

    • Neutral: No significant change in functionality.

    • Beneficial: Enhancements in infectivity or the ability to evade host immune responses.

    • Deleterious: Loss of infectivity often leading to attenuated strains used in vaccine development.

Antigenic Drift and Antigenic Shift

  • Following infection or vaccination against influenza, the host immune system recognizes the HA and NA spikes as antigens, developing specific antibodies targeting them.

  • Antigenic drift: Refers to frequent mutations within the RNA genome of influenza, resulting in minor changes to the HA and NA spikes.

  • Antigenic shift: Refers to significant genetic reassortment events within influenza which may lead to new viral strains with increased infectivity or expanded host range.

    • In cases of antigenic shift, humans often have no residual immune protection from past infections or vaccinations, potentially setting the stage for pandemics.

6.2: Classifying and Naming Viruses

  • Diverse Features are Used to Classify and Name Viruses

    • Viruses are classified by the following properties:

    • Type of nucleic acid present (DNA or RNA)

    • Capsid symmetry (helical, icosahedral, or complex)

    • Presence or absence of an envelope

    • Genome architecture (ssDNA, ssRNA, etc.)

Host Range and Tropism

  • Host range: Refers to the collection of species that a virus can infect.

    • Some viruses can infect multiple species (e.g., Zoonotic viruses), while others are species-specific (e.g., measles virus which only infects humans).

  • Tropism: Refers to the specificity of tissues or cells that a virus may infect.

    • Some viruses have a broad tropism, being able to infect a wide range of host cells, while others have a narrower tropism, affecting only specific tissue types.

Virus Sizes

  • Viruses display a large variability in size:

    • Rhinoviruses and polioviruses can have a diameter as small as 30 nm.

    • Ebola virus reaches lengths nearing 1,000 nm.

    • Pithovirus, discovered in 2014, is one of the largest viruses, measuring approximately 1,500 nm.

6.3: Viral Replication Pathways

  • Viruses Hijack Host Cell Machinery to Multiply

    • Once a virus enters a host cell, it commandeers the cell's energy, enzymes, organelles, and molecular building blocks to assemble new virions.

Bacteriophages & Their Replication Process

  • Lytic Replication

    • Involves lytic phages infecting a host bacterial cell and immediately initiating the construction of new virions, culminating in the death of the host cell as new bacteriophages are released.

    • Steps include:

    1. Attachment (adsorption): Phage binds to bacterial cell.

    2. Penetration (entry): Phage injects its genetic material into the bacterial cell.

    3. Replication (synthesis): Phage utilizes host cell factors to transcribe and translate its viral genes.

    4. Assembly (maturation): The viral genome is encapsulated into the capsid and phage structures are assembled.

    5. Release: The bacterial cell lyses, releasing new phages.

  • Lysogenic Replication

    • Performed by temperate phages:

    • Steps include:

    1. Attachment and Penetration: Similar to lytic phase.

    2. The phage genome incorporates into the host cell’s genome, forming a prophage.

    3. As the host cell divides, the prophage is replicated alongside the host’s genome.

    4. If the host cell experiences stress, the prophage may excise itself from the host genome and enter the lytic replication pathway.

    • Phage conversion: Prophages can endow new pathogenic properties to bacterial cells (e.g., toxins).

    • Examples include:

      • Corynebacterium diphtheriae

      • Clostridium botulinum

Generalized Animal Virus Replication

  • The general animal virus replication pathway consists of six steps:

    1. Attachment: Naked viruses attach to host cell membranes via capsid proteins or spikes.

    2. Penetration:

    • Enveloped viruses enter through endocytosis or membrane fusion.

    • Naked viruses typically enter via endocytosis.

    1. Uncoating: The capsid is digested by enzymes within the endocytic vesicle or the cytoplasm/nucleus.

    2. Replication (Synthesis): The viral genome replicates and viral proteins are synthesized.

    3. Assembly: Newly formed virions are assembled.

    4. Release: Released in two manners:

    • Enveloped viruses are released by budding.

    • Naked viruses rupture the host cell during release.

Some Animal Viruses Have Unique Replication Mechanisms That Cause Persistent Infections

  • Acute infections: Viruses infect a host cell and generate new virions immediately.

  • Persistent infections: Viruses adopt replication strategies that permit them to evade immune system clearance.

    • Chronic Persistent Infections: Characterized by consistent release of virions over time (months or years) and slow disease progression, e.g., HIV where the viral genome integrates into the host cell to form a provirus.

    • Latent Persistent Infections: Marked by flare-ups with periods of dormancy (latency). During flare-ups, virions are shed and symptoms occur, potentially triggered by factors such as stress, fever, sunburn, or hormone level changes.

    • Notable members of the Herpesviridae family that cause latent infections:

    • Human herpes virus-1 (HSV-1): Causes cold sores.

    • Human herpes virus-2 (HSV-2): Causes genital herpes.

    • Varicella-zoster virus (HHV-3): Causes chickenpox and shingles.

Persistent Infections That Can Lead to Cancer

  • Oncogenic viruses (oncoviruses): Defined as viruses capable of inducing cancer.

    • Responsible for approximately 10-15% of all cancers.

    • Mechanisms of causing cancer:

    • Stimulation of uncontrollable host cell division.

    • Decreasing host cell responsiveness to intrinsic death signals.

    • Example: Human papillomaviruses (HPVs).

6.5: Prions

  • Definition of Prions: Infectious proteins that lack genetic material and do not replicate in a traditional sense.

  • Effect on Health: Prions cause transmissible spongiform encephalopathies (TSEs), which are neurodegenerative diseases characterized by sponge-like changes in the brain tissue.

  • Spongiform Encephalopathies: Can be inherited or acquired, examples include:

    • Inherited forms:

    • Gerstmann-Straussler-Scheinker syndrome

    • Fatal familial insomnia

    • Acquired forms:

    • Creutzfeldt-Jakob disease (CJD), with variant (vCJD) as a sporadic and iatrogenic form.