Viruses and Prions: Structure, Replication, and Pathogenicity

Viruses and Prions

Introduction

Viruses and prions are unique infectious agents that differ fundamentally from cellular life forms. This chapter explores their structure, replication, classification, and roles in disease, with a focus on their medical relevance.

Host Range and Viral Entry

Host Range

• Host range refers to the spectrum of host cells a virus can infect. This is determined by the compatibility between viral surface proteins and host cell receptors.

• Some viruses have a narrow host range (e.g., HIV infects only humans), while others have a broad host range (e.g., rabies virus infects many mammals).

Role of Receptors

• Viruses attach to specific receptors on the host cell surface, which determines cell and tissue tropism.

• Without the appropriate receptor, a virus cannot enter or infect the cell.

Basic Features of Viruses

Virion Structure

• A virion is a complete, infectious viral particle outside a host cell.

• Key components include:

  • Capsid: Protein coat protecting the viral genome.

  • Capsomeres: Protein subunits that make up the capsid.

  • Nucleic acid: Either DNA or RNA, single- or double-stranded.

  • Envelope (in some viruses): Lipid membrane derived from the host cell, containing viral proteins.

  • Spikes: Glycoprotein projections involved in host cell recognition and attachment.

Capsid Shapes

• Helical: Rod-shaped, with nucleic acid inside a helical capsid (e.g., tobacco mosaic virus).

• Polyhedral: Many-sided, often icosahedral (e.g., adenovirus).

• Complex: Complicated structures, often with additional components (e.g., bacteriophages).

Envelope and Immune Evasion

• The envelope helps viruses evade the immune system by mimicking host cell membranes.

• Enveloped viruses (e.g., influenza, HIV) are generally more sensitive to environmental conditions than naked (non-enveloped) viruses (e.g., poliovirus, adenovirus).

Comparison of Enveloped and Naked Viruses

Feature	Enveloped Virus	Naked Virus
Structure	Lipid envelope + capsid	Capsid only
Examples	Influenza, HIV	Poliovirus, Adenovirus
Environmental Stability	Less stable	More stable
Immune Evasion	Better (mimics host)	Poorer

Taxonomy and Classification of Viruses

Viral Taxonomy

• Viruses are classified based on nucleic acid type, replication strategy, morphology, and host range.

• Families end in -viridae, genera in -virus.

Viral Species and Subspecies

• A viral species is a group of viruses sharing the same genetic information and ecological niche.

• Subspecies are designated by numbers or letters (e.g., HSV-1, HSV-2).

Growth and Cultivation of Viruses

Challenges in Growing Animal Viruses

• Viruses require living cells for replication, making cultivation challenging.

• Common methods:

  • In animals: Used for studying pathogenesis and immune response.

  • In embryonated eggs: Used for vaccine production (e.g., influenza vaccine).

  • In cell cultures: Most common; involves growing viruses in monolayers of animal cells.

Viral Multiplication Cycles

Lytic Cycle of Bacteriophages

• The lytic cycle results in the destruction of the host cell and release of new virions.

• Phases:

  1. Attachment: Phage attaches to host cell.

  2. Penetration: Phage injects DNA into host.

  3. Biosynthesis: Phage DNA directs synthesis of viral components.

  4. Maturation: Assembly of phage particles.

  5. Release: Host cell lyses, releasing new phages.

Lysogenic Cycle

• In the lysogenic cycle, phage DNA integrates into the host genome as a prophage.

• The prophage is replicated with the host cell and can later enter the lytic cycle.

• Possible outcomes include immunity to superinfection and transfer of new traits to the host (lysogenic conversion).

Animal Virus Replication

• Phases:

  1. Attachment: Virus binds to host cell receptors.

  2. Entry: By endocytosis or fusion.

  3. Uncoating: Viral genome released.

  4. Biosynthesis: Viral genome replicated and proteins synthesized.

  5. Maturation: Assembly of virions.

  6. Release: By budding (enveloped viruses) or lysis (naked viruses).

• Budding allows enveloped viruses to exit without killing the host cell, while lysis destroys the cell.

Categories of Viral Infections

• Acute infection: Rapid onset, short duration (e.g., influenza).

• Latent infection: Virus remains dormant, can reactivate (e.g., herpes simplex virus).

• Persistent (chronic) infection: Virus continuously present (e.g., hepatitis B).

Replication of DNA and RNA Viruses

DNA Virus Replication

• Usually replicate in the host cell nucleus using host enzymes.

• Viral DNA → mRNA → viral proteins.

RNA Virus Replication

• Replication occurs in the cytoplasm.

• RNA-dependent RNA polymerase synthesizes RNA from an RNA template.

• Sense (+) strand RNA viruses: Genome acts as mRNA.

• Antisense (-) strand RNA viruses: Genome is complementary to mRNA; must be transcribed to (+) RNA first.

• Retroviruses (e.g., HIV): Use reverse transcriptase to convert RNA to DNA, which integrates into the host genome as a provirus.

Retrovirus replication pathway:

$\text{RNA} \xrightarrow{\text{reverse transcriptase}} \text{DNA} \rightarrow \text{mRNA} \rightarrow \text{Protein}$

Viruses and Cancer

• Some viruses can cause cancer by integrating their genome into host DNA, disrupting normal cell regulation.

• Oncogenes: Genes that can transform a normal cell into a cancerous cell.

• Oncogenic viruses: Viruses capable of inducing tumors (e.g., human papillomavirus, Epstein-Barr virus).

• Formation of a provirus can lead to uncontrolled cell division and tumor growth.

Examples of Virus-Associated Cancers

• Human papillomavirus (HPV): Cervical cancer

• Hepatitis B and C viruses: Liver cancer

• Epstein-Barr virus: Burkitt's lymphoma

Medically Important Viruses

Influenza Virus

• Transmitted via respiratory droplets.

• Key surface proteins:

  • Hemagglutinin (HA): Binds to host cell receptors.

  • Neuraminidase (NA): Facilitates release of new virions.

• Annual vaccination is necessary due to frequent antigenic changes (antigenic drift and shift).

• Health consequences include pneumonia, secondary bacterial infections, and death in vulnerable populations.

Ebola Virus

• Causes severe hemorrhagic fever with high mortality rates.

• Transmitted through contact with bodily fluids.

• Major concern in healthcare settings due to rapid spread and lack of specific treatments.

Viroids and Prions

Viroids

• Viroids are small, circular RNA molecules that infect plants.

• Lack a protein coat and do not encode proteins.

• Cause diseases such as potato spindle tuber viroid.

Prions

• Prions are infectious proteins that cause neurodegenerative diseases.

• Examples: Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (mad cow disease).

• Prions propagate by inducing misfolding of normal proteins, leading to cell damage and characteristic spongiform changes in the brain.

Additional info: Prions lack nucleic acids and are resistant to standard methods of inactivation, making them particularly challenging in healthcare settings.