Understanding Virology: Acronyms, Concepts, and Vaccines

Acronyms in Virology

  • AIDS: Acquired immunodeficiency syndrome
  • ART: Antiretroviral therapy
  • ccc: Covalently closed circle
  • CMV: Cytomegalovirus
  • CPE: Cytopathic effects
  • CTL: Cytotoxic T lymphocyte
  • DLP: Double-layered particle
  • EBV: Epstein-Barr virus
  • ER: Endoplasmic reticulum
  • ESCRT: Endosomal sorting complexes required for transport
  • GFP: Green fluorescent protein
  • HA: Hemagglutinin
  • Hsp60: Heat shock protein 60
  • ICAM-1: Intercellular adhesion molecule
  • IFN: Interferon
  • IHF: Integration host factor
  • IRES: Internal ribosome entry site
  • LTR: Long terminal repeat
  • LUCA: Last universal common ancestor
  • NA: Neuraminidase
  • NCCR: Noncoding control region
  • PABP: Poly(A)-binding protein
  • PBS: Primer-binding site
  • Pol II: RNA Polymerase II
  • PRR: Pattern recognition receptor
  • RdRp: RNA-dependent RNA polymerase
  • RF: Replicative form
  • RNAP: RNA polymerase
  • RSV: Respiratory syncytial virus
  • SARS: Severe acute respiratory syndrome
  • SEM: Scanning electron microscopy
  • sgRNA: Subgenomic RNA
  • TAP: Transporter associated with antigen processing
  • TCR: T-cell receptor
  • TEM: Transmission electron microscopy
  • TF: Tissue factor
  • TH: T helper
  • TMV: Tobacco mosaic virus
  • TRS: Transcription regulatory sequence
  • UTR: Untranslated region
  • VGF: Vaccinia growth factor
  • VLP: Virus-like particles
  • VP: Viral protein
  • VPg: Viral protein genome-linked
  • vRNP: Viral ribonucleoprotein complex
  • VSV: Vesicular stomatitis virus
  • VZV: Varicella-zoster virus

Key Virology Concepts and Definitions

  • Capsid: Protein shell enclosing the viral genome.
  • Envelope: Lipid layer surrounding some viruses, containing glycoproteins.
  • Replication Mechanisms: Includes RdRp, reverse transcription, cap snatching, etc.
  • Host Range: Species a virus can infect.
  • Tissue Tropism: Specific tissues a virus targets.
  • Latency: Dormant period where the virus does not replicate (e.g., herpesviruses).
  • Lysogeny: Bacteriophage integrates genome into host DNA (prophage state).
  • Reverse Transcription: RNA to DNA conversion (used by retroviruses).
  • Vaccines: Induce immunity; types include live-attenuated, inactivated, protein-based.
  • Antiviral Drugs: Target specific replication stages to inhibit viral activity.

Polio Vaccines

  • Description: Developed to prevent poliomyelitis (polio), caused by the poliovirus.
  • Types:
    1. Oral Polio Vaccine (OPV):
      • Contains live attenuated poliovirus.
      • Administered orally.
      • Provides strong intestinal immunity but may rarely revert to a virulent form.
      • Developed by Albert Sabin in the 1960s.
    2. Inactivated Polio Vaccine (IPV):
      • Contains inactivated (killed) poliovirus.
      • Administered via injection.
      • Safer than OPV; developed by Jonas Salk in 1955.
    3. Novel Oral Polio Vaccine Type 2 (nOPV2):
      • Modified version of OPV.
      • Engineered to have reduced risk of reversion to virulence.
      • Designed to combat outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2).

The Early Smallpox Vaccine (Jenner’s Vaccine)

  • Developer: Edward Jenner, 1796.
  • Composition: Used material (pus) from cowpox lesions. Cowpox (Vaccinia virus) is closely related to the smallpox virus (Variola virus).
  • Mechanism:
    • Cowpox virus infection is mild in humans but generates immunity against smallpox because of antigenic similarities.
    • Jenner’s method relied on introducing the cowpox virus through a process called variolation or vaccination.
  • Effectiveness: Provided robust immunity with a much lower risk than contracting smallpox itself.
  • Historical Importance: This was the first vaccine in history, marking the beginning of immunology.

Second-Generation Smallpox Vaccines

  • Composition: Refined versions of the Vaccinia virus.
    • Dryvax: Lyophilized (freeze-dried) vaccine developed in the 20th century.
      • Easier to store and transport compared to earlier liquid formulations.
      • Standardized for mass production.
  • Improvements:
    • Safer and more effective than Jenner’s original formulation.
    • Allowed for more efficient vaccination campaigns.
  • Administration:
    • Typically delivered using a bifurcated needle, which reduced the amount of vaccine needed while ensuring efficacy.

Third-Generation Smallpox Vaccines

  • Modern Variants:
    • ACAM2000: A modern live Vaccinia virus vaccine derived from Dryvax. Used primarily for military personnel and emergency preparedness.
    • MVA-BN (Modified Vaccinia Ankara):
      • A highly attenuated form of the Vaccinia virus, incapable of replication in human cells.
      • Safer for individuals with compromised immune systems or certain health conditions.
  • Focus: These vaccines were developed for bioterrorism preparedness and are used for specific populations at risk.

How Smallpox Vaccines Led to Eradication

  1. Effective Immunity:
    • Vaccines provided durable immunity against smallpox by triggering a strong adaptive immune response to the Vaccinia virus.
    • Cross-protection between cowpox (Vaccinia) and smallpox (Variola) was key.
  2. Global Vaccination Campaign:
    • World Health Organization (WHO) Campaign: Launched in 1959, intensified in 1967.
    • Focused on mass vaccination programs in endemic regions.
    • Vaccination efforts were coupled with surveillance and containment strategies.
  3. Ring Vaccination:
    • Strategy of vaccinating people in the immediate vicinity of an identified case, creating a “ring” of immunity around outbreaks.
    • This approach minimized the spread of the virus and was critical in areas where mass vaccination was logistically challenging.
  4. Stability of the Vaccine:
    • Lyophilized vaccines like Dryvax were highly stable, enabling distribution in remote regions with limited refrigeration.
  5. Absence of an Animal Reservoir:
    • Smallpox only infects humans, simplifying eradication efforts since no animal reservoirs needed to be addressed.
  6. Visible Symptoms:
    • Smallpox cases were easy to identify due to characteristic pustular rashes, aiding in rapid containment.
  • In 1980, the WHO declared smallpox eradicated worldwide, making it the first human disease to be eradicated through vaccination.

Class I: dsDNA Viruses

  • Genome: Double-stranded DNA; replication via DNA-dependent DNA polymerase (host or viral).
  • Examples:
    • Human Herpesvirus 1: Establishes latency in neurons, reactivates to cause recurrent infections.
    • Bacteriophage T7: Infects E. coli, encodes its own polymerase for replication.
    • Bacteriophage Lambda: Can integrate into the host genome as a prophage or replicate lytically.

Class II: ssDNA Viruses

  • Genome: Single-stranded DNA converted to dsDNA by host DNA polymerase for replication.
  • Examples:
    • Porcine Circovirus 2: Infects pigs with a circular ssDNA genome.
    • Bacteriophage ΦΧ174: First sequenced DNA genome, uses overlapping genes.
    • Bacteriophage M13: Filamentous, replicates via rolling-circle mechanism.

Class III: dsRNA Viruses

  • Genome: Double-stranded RNA; uses packaged RNA-dependent RNA polymerase (RdRp) for transcription.
  • Examples:
    • Rotavirus: Major cause of gastroenteritis, segmented genome.

Class IV: (+) ssRNA Viruses

  • Genome: Positive-sense RNA acts as mRNA; RdRp synthesizes a (-) RNA intermediate for replication.
  • Examples:
    • Zika Virus: Mosquito-borne, causes congenital defects.
    • Coronavirus (e.g., SARS-CoV-2): Causes COVID-19.
    • Polio Virus: Can cause paralysis.
    • Dengue Virus: Mosquito-borne, causes fever and pain.

Class V: (-) ssRNA Viruses

  • Genome: Negative-sense RNA; requires RdRp to produce mRNA.
  • Examples:
    • Influenza Virus: Causes seasonal flu, segmented genome.
    • Ebola Virus: Causes hemorrhagic fever.
    • Lassa Fever Virus: Spread by rodents, causes hemorrhagic fever.

Class VI: (+) ssRNA, Retroviruses

  • Genome: Positive-sense RNA reverse-transcribed into DNA, integrates into the host genome.
  • Examples:
    • HIV: Infects and destroys CD4+ T cells, causes AIDS.

Class VII: dsDNA, Reverse-Transcribing Viruses

  • Genome: Partially double-stranded DNA; reverse transcription of an RNA intermediate completes replication.
  • Examples:
    • Hepatitis B: Infects the liver, can lead to chronic disease and cancer.