6a

Acellular Pathogens: Viruses and Prions

Study Guide

• List key unique features (or lack thereof) of viruses

• Explain how a virus can be considered to be non-living, yet infectious

• Define virus host range and tissue/cellular tropism

• Review the central dogma of molecular biology

• Compare replication mechanisms of DNA containing, and RNA containing,

viruses

• Explain methods of virus cultivation

• Describe potential targets of clinical anti-viral therapies

Unique Features of Viruses

Viruses are characterized by several unique features which set them apart from cellular life forms:

  • Nature of Composition: Viruses consist of a core of genetic material (either DNA or RNA, but never both) surrounded by a protein coat known as a capsid.

  • Presence of an Envelope: Some viruses are enveloped, possessing an outer lipid layer obtained from the host cell membrane when the virus buds off during replication.

  • Obligate Intracellular Parasites: Viruses cannot replicate independently; they must infect a host cell and hijack its cellular machinery for reproduction.

Non-Living Yet Infectious

Despite their infectious nature, viruses can be considered non-living based on specific criteria:

  • Lack of Cellular Structures: Viruses do not possess cellular machinery such as ribosomes, making them incapable of sustaining life independently.

  • Replication Dependency: They can only replicate inside a living cell (the host) using that cell's biological processes.

Virus Host Range and Tissue/Cellular Tropism

  • Host Range: This refers to the range of host species that a virus can infect. For example, the poliovirus infects humans only, whereas the rabies virus can infect most warm-blooded animals.

  • Tissue Tropism: This is the preference of a virus for certain tissues or organs within the host, often influenced by viral surface proteins that interact with specific cell receptors.

Central Dogma of Molecular Biology

The central dogma outlines the flow of genetic information within a biological system:

  1. DNA is Transcribed: Into messenger RNA (mRNA).

  2. mRNA is Translated: Into a functional protein at the ribosome.

Comparison of Replication Mechanisms of DNA and RNA Viruses

DNA Viruses

The replication process typically includes:

  1. Attachment/Entry: Virus binds to host cell.

  2. Uncoating: Viral capsid is removed.

  3. Biosynthesis:

    • DNA Synthesis

    • Protein synthesis

  4. Maturation/Assembly: New virions are assembled.

  5. Egress/Exit: New viruses exit the host cell.

  • Example: Varicella Zoster Virus (VZV)

RNA Viruses

The replication process typically involves:

  1. Attachment/Entry

  2. Uncoating

  3. Biosynthesis:

    • RNA synthesis (which is more error-prone than DNA synthesis)

    • Protein synthesis

  4. Maturation/Assembly

  5. Egress/Exit

  • Example: Corona viruses

Methods of Virus Cultivation

Various techniques are employed to cultivate viruses, including:

  1. Cell Culture: Using flasks or plates containing human or animal cells; clear plaques indicate viral replication.

  2. Chicken Eggs: Different types of viruses can be cultivated within specific areas of chicken eggs, such as the chorioallantoic membrane and the yolk sac.

  3. Primary and Continuous Cell Cultures: Primary cultures have contact inhibition, while continuous cultures grow indefinitely regardless of density.

Targets of Clinical Anti-Viral Therapies

Potential targets include viral proteins necessary for replication and assembly, as well as host cell processes that can be inhibited to prevent viral infection.

Representative Viruses and Associated Diseases

  • Varicella Zoster Virus: Causes chickenpox (varicella) and can lead to shingles (zoster) later in life.

  • SARS-CoV-2: Causes COVID-19; infects respiratory epithelial cells and can result in severe respiratory distress.

  • Influenza Virus: Causes seasonal flu; characterized by high mutation rates.

  • HIV: Causes AIDS and attacks the immune system, particularly CD4+ T cells.

Mechanisms of Prion Pathology and Transmission

Prions are misfolded proteins that induce normal proteins to misfold, resulting in transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease. They can be transmitted through infected tissues or medical procedures (iatrogenic).

Historical Discovery of Viruses

  • 1892: Dmitri Ivanovsky discovered that the infectious agent causing tobacco mosaic disease could pass through filters designed to trap bacteria, illustrating that the agent was not a bacterium.

  • 1898: Martinus Beijerinck further investigated the substance, determining it was not a bacteria, coining the term "virus" which translates to "poison" in Latin.

  • 1915/1917: Frederick William Twort and Felix d’Herelle discovered bacteriophages, viruses that infect and destroy bacteria.

  • 1941: The advent of the electron microscope allowed the visual observation of viruses for the first time.

Virus Taxonomy

Viruses are classified into families identified by the suffix "-viridae" and genera classified by the suffix "-virus." Individual types often have common names that are not italicized, such as Flaviviridae (the family) and Flavivirus (the genus), which includes the Yellow Fever Virus.

Cytopathic Effects of Viral Infections

  • Host Cell Damage: Infections can lead to various cellular changes, some of which include:

    1. Cytocidal effects leading to cell death

    2. Syncytia formation where infected cells fuse to form multinucleated giant cells

    3. Inclusion bodies where viral proteins aggregate within the cytoplasm.

    4. Damage to the immune system, causing inflammatory responses.

    5. Inducing apoptosis (programmed cell death).

Potential Viral-Induced Cancers

About 20% of tumors are associated with viral infections, highlighting the oncogenic potential of some viruses.

The Updated Central Dogma of Molecular Biology

This concept reflects the complexity of viral replication mechanisms that utilize RNA-dependant RNA polymerase and reverse transcriptase.

Vaccines and Prevention Strategies

Vaccination is key in preventing viral infections. Examples of current vaccines include:

  • SARS-CoV-2 Vaccines: Various strategies include non-replicating viral vectors, mRNA-based vaccines (e.g., Pfizer and Moderna), and inactivated virus vaccines.

  • Varicella Vaccine: The Varivax vaccine has been in use since 1995 to prevent chickenpox and shingles.

  • Influenza Vaccine: This seasonal vaccine includes killed virus preparations to protect against the prevalent strains of influenza.

Specific Viral Case Studies

Varicella Zoster Virus

  • Characteristics: Double-stranded DNA, enveloped virus, causes chickenpox and potential for later shingles.

  • Transmission: Mainly through inhaled droplets, can also occur via skin contact.

  • Epidemiology: Once infected, the virus remains dormant in the host's neurons for life.

SARS-CoV-2

  • Characteristics: Single-stranded RNA virus, responsible for COVID-19.

  • Pathogenesis: Infects lung epithelial cells leading to respiratory distress and systemic complications.

Influenza Virus

  • Characteristics: Segmented (-) RNA virus; airborne transmission.

  • Pathogenesis: Causes opportunistic infections and severe symptoms, with annual deaths due to complications like pneumonia.

HIV Infection and Progression

HIV primarily infects immune cells and leads to AIDs over time, characterized by stages of infection:

  • Stage I: Asymptomatic or flu-like symptoms shortly after infection.

  • Stage II: Clinical latency, where individuals are usually asymptomatic but the virus slowly spreads.

  • Stage III: Initial HIV symptoms emerge, indicating immune system decline.

  • Stage IV: Development of AIDS, marked by severe immune impairment, with opportunistic infections occurring.

Prions

Prions are infectious proteins that cause neurodegenerative diseases through the misfolding of normal cellular proteins. They can be transmitted through medical procedures and cause conditions like Creutzfeldt-Jakob disease (CJD).