Virology

Virology

1. Morphology

   • Core components
     • Nucleic acid core: Contains DNA or RNA genome
     • Capsid: Protective outer protein coating
       • Capsomeres: Individual protein subunits that form the capsid
     • Envelope: Phospholipid bilayer derived from host cell membranes
     • Additional proteins: enzymes or matrix proteins (stablise the envelope)
     • Glycoproteins: Surface "spikes" used to attach to host cell receptors
   • Structural Classifications
     • Filamentous: Long, thin, and cylindrical (e.g., Tobacco Mosaic Virus)
     • Isometric / Icosahedral: Roughly spherical or polyhedral (e.g., Poliovirus, Herpes)
     • Enveloped: Capsid nested inside a membrane (e.g., HIV, Flu, Mumps).
     • Head and Tail: Complex hybrid structure; icosahedral head + cylindrical tail (e.g., T4 Bacteriophage).
   • Attachment & Infection
     • Viral Receptors: Normal cell surface molecules (like CD4) hijacked by viruses
     • Glycoprotein Interaction: Must bind to host molecules to penetrate the cell
     • Host Complexity: The complexity of the virus does not match the complexity of the host.
   • Resilience & Classification
     • Enveloped vs. Non-Enveloped
       • Enveloped: Fragile; sensitive to temperature and pH.
       • Non-Enveloped: Hardier; resistant to disinfectants and environmental changes

2. Types of Nucleic Acids

   • Either DNA or RNA
     • Single-stranded (ss) or Double-stranded (ds)
     • Linear or Circular
   • Segmentation: May be a single nucleic acid or multiple pieces called segments
   • DNA Viruses Mechanism: Hijacks host cell proteins to replicate the viral genome and synthesize proteins.
   • RNA Viruses
     • Mechanism
       • Must encode their own enzymes (like RNA polymerase) to replicate RNA; the host cell cannot do this.
     • Mutation Rate
       • High; RNA polymerase makes more copying errors than DNA polymerase.
     • Adaptation
       • Frequent mutations allow them to change and adapt to hosts more rapidly.

3. Virus Classification

   • Traditional Classification Factors
     • Core Content: Type of genetic material (DNA/RNA) and its structure (ss/ds, linear/circular, segmented)
     • Capsid Design: Classified into five main categories
       • Naked icosahedral
       • Enveloped icosahedral
       • Naked helical
       • Enveloped helical
       • Complex
   • The Baltimore Classification Scheme

4. Viral Infection and Replication

   • The Nature of Infection
     • Obligate Intracellular Parasites: Viruses must enter a living cell to function
     • Permissive Cells: Only specific cells allow a virus to replicate
     • Specificity: Determined by "Lock and Key" fit between viral proteins and host receptors.
     • Host Range: Limited to certain species and specific cell types based on gene expression
   • Stages of Replication
     • 1) Attachment: Viral proteins or glycoproteins bind to specific host membrane receptors.
     • 2) Entry (Penetration):Bacteriophages: a) Inject "naked" nucleic acid, leaving the capsid outside. b) Animal/Plant Viruses: Enter via endocytosis (engulfment) or fusion (envelope merges with cell membrane).
     • 3) Uncoating: The viral capsid is degraded, releasing the genome into the cell
     • 4) Replication: a) DNA Viruses: Usually use host enzymes to make DNA and mRNA. b) RNA Viruses: Use the RNA core as a template for new genomes and mRNA. c) Retroviruses (e.g., HIV): Use reverse transcriptase to turn RNA into DNA for host integration.
     • 5) Assembly: Host cell synthesizes viral enzymes and capsids, then packages the new virions
     • 6) Egress (Release): New virions exit to infect adjacent cells
   • Cellular Impact (Cytopathic Effects)
     • Lysis: The cell bursts and dies instantly (e.g., Rhinovirus)
     • Apoptosis: Programmed "cell suicide" triggered by infection
     • Budding: Virions exit individually (e.g., HIV). The cell stays alive temporarily but loses normal function
     • Symptoms: Caused by both direct cell damage and the body’s own immune response
   • The Process and the Impact
     • The Process (The "How")
       • The Replication Cycle: Uncoating: Stripping the protein shell to expose the "blueprints." Synthesis: Forcing the host to build viral proteins and copy the genome. Reverse Transcription: (Retroviruses only) Converting RNA into DNA to hide in the host's genome.
       • Targeting: Finding permissive cells using a "lock and key" receptor match.
       • Exit Strategies: Budding: Leaving one by one through the membrane (common in enveloped viruses). Lysis: Forcing the cell to burst to release all "offspring" at once
       • Entry Methods: Injection: Only the genome enters (Bacteriophages). Endocytosis: The cell membrane swallows the whole virus. Fusion: Viral envelope blends into the cell membrane.
     • The Impact (The "Result")
       • Medical Intervention: Development of drugs (like AZT) that target virus-only enzymes to stop the process without harming the host.
       • Disease Symptoms: A combination of direct cell damage and the body's immune response (inflammation, fever, etc.).
       • Cell Death: Lysis: Immediate destruction of the cell. Apoptosis: The cell is triggered to commit "suicide."
       • Functional Loss: Cells that survive (via budding) often become "zombies" that can no longer perform their normal physiological jobs.
       • Cytopathic Effects (CPE): Physical damage or structural changes to the host cell.

5. Bacteriophages vs. Animal Viruses

   • Bacteriophage
     • Replication
       • Productive Infection: Results in the creation of new virions.
       • Lytic Cycle: The virus replicates immediately and destroys the host cell by bursting (lysis). Example: T4 phage (infects E. coli)
       • Lysogenic Cycle: The viral DNA is incorporated into the host genome (now called a prophage).The virus remains silent and replicates as the bacteria divides. Example: (lambda) phage.
   • Animal Virus
     • Animal Virus Entry & Exit
       • No Cell Wall: Animal viruses do not need to penetrate a rigid wall.
       • Entry Methods: Non-enveloped: Enter via receptor-mediated endocytosis or by creating protein channels to "inject" the genome. Enveloped: Enter via endocytosis or fusion (viral envelope merges with the cell membrane).
       • Exit Methods: Budding: Enveloped viruses take a piece of the host membrane as they leave (e.g., HIV). Lysis: Non-enveloped viruses accumulate until the cell bursts (e.g., Rhinovirus).
     • Types of Animal Infections
       • Acute: Rapid onset of symptoms, followed by recovery as the immune system clears the virus (e.g., Influenza, Common Cold).
       • Asymptomatic: Productive infection occurs but the host shows no symptoms (e.g., Roseola).
       • Chronic: Long-term, low-level virus production. Often escapes the immune system for years (e.g., Hepatitis C)
         • Key Differences at a GlanceVirus Presence: Acute is "hit and run"; Chronic is "stay and play."Symptoms: Acute symptoms are often intense but brief; Chronic symptoms are often invisible until significant damage is done.Detection: Acute is usually found via symptoms; Chronic is often found via routine blood work.
       • Latent: Virus "hides" in tissue (e.g., nervous tissue) without producing virions for long periods.Can reactivate due to stress (e.g., Herpes Simplex, Shingles)
     • Oncogenic Viruses
       • Mechanism: Interfere with the host cell cycle by introducing growth-stimulating genes (oncogenes) or blocking growth inhibitors.
       • Associated Cancers: HPV: Cervical cancer. Hepatitis B & C: Liver cancer .Other: T-cell leukemia and lymphomas

6. Prevention & Treatment

   • Antiviral Drugs
     • Mechanism: Block specific viral proteins/enzymes without harming host cells.
     • Mechanism: Block specific viral proteins/enzymes without harming host cells. Success Stories: Acyclovir: Reduces herpes outbreaks (does not cure latency). Tamiflu: Blocks neuraminidase to stop flu virions from leaving cells (shortens illness). Ribavirin: A general antiviral used for various infections
   • Vaccines for Treatment
     • Ebola: New vaccines help the body control this rapid, high-fatality virus
     • Rabies: Because the virus travels slowly to the nervous system, post-bite vaccination can stop it in time.
     • The Concept: Boosting the immune system after exposure to fight an active infection.
   • HIV & HAART
     • The Challenge: HIV mutates rapidly, making it easy to develop resistance to single drugs.
     • HAART (Highly Active Anti-Retroviral Therapy): A "cocktail" of drugs attacking different stages of the cycle:
       • Fusion Inhibition: Prevents the HIV viral envelope from merging with the host's plasma membrane; stops the virus from entering.
       • Integrase Inhibition: Prevents the newly formed viral DNA from being inserted into the host's own genome
       • Reverse Transcriptase Inhibition: Blocks the conversion of viral RNA into double-stranded DNA; stops the "blueprint" from being created.
       • Protease Inhibition: Blocks the final processing of viral proteins; prevents the assembly of functional, infectious new virions
     • Result: Turns a fatal disease into a manageable, long-term condition
   • Vaccines for Prevention
     • Primary Goal: Build immunity to prevent outbreaks before they occur.
     • Types of Vaccines: Live Attenuated: Weakened "wild-type" virus. Most effective but carries a tiny risk of back mutation (reverting to disease-causing form). Killed/Inactivated: Dead virus; cannot cause disease. Molecular Subunits: Only pieces of the virus; cannot cause disease
       • Live Attenuated Vaccines:
         • Cons: Small risk of back mutation (virus reverts to disease-causing form)
         • Example: Oral Polio vaccine, Measles, Mumps
         • Method: Uses a "wild-type" virus weakened in a lab (via different temperatures or tissues)
         • Pros: Highly effective; creates a strong, long-lasting immune response
       • Killed / Subunit Vaccines:
         • Pros: Safe; impossible for the vaccine to cause the actual disease
         • Cons: Often less effective than live versions; may require booster shots
         • Example: Original Salk Polio vaccine, seasonal Influenza
         • Method: Uses a completely destroyed virus or just specific molecular pieces
     • Mutation Challenges: Low Mutation: Vaccines for measles/mumps stay effective for years. High Mutation: Influenza requires a new vaccine annually to keep up with surface protein changes.

7. Other Acellular Entities: Prions

   • Pirons
     • No Genetic Material: Contain no DNA or RNA (unique among infectious agents).
     • Diseases:
       • BSE ("Mad Cow Disease"): Found in cattle; spread via infected feed
       • Kuru: Found in humans; spread via ritualistic cannibalism
       • Variant CJD: Human version acquired by eating BSE-infected beef
     • Characteristics: Deadly, difficult to treat, and resistant to standard sterilization
     • Mechanism of Infection:
       • PrP: The normal cellular protein PrP^c
       • Chain Reaction: PrP^sc binds to normal PrP^c and converts it into the infectious form.
       • Variant: The infectious, abnormally folded form PrP^sc
       • Accumulation: Abnormal proteins aggregate, causing "holes" or lesions in brain tissue.
     • Structure: Simpler than viruses; consist entirely of protein.
   • Prions Vs Viruses
     • Prions: Protein only (No nucleic acid)
     • Viruses: Nucleic acid (DNA/RNA) + Protein coat

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