Virology Notes

Virology (BIO 352)

Grading System

  • Four (4) exams: 400 points
  • Ten (10) quizzes: 100 points
  • Total: 500 points
  • Grading Scale:
    • 1. 0: 97-100 (Excellent)
    • 1. 25: 94-96 (Excellent)
    • 1. 5: 91-93 (Very Good)
    • 1. 75: 88-90 (Very Good)
    • 2. 0: 85-87 (Good)
    • 1. 25: 82-84 (Good)
    • 2. 5: 79-81 (Satisfactory)
    • 1. 75: 76-78 (Satisfactory)
    • 3. 0: 75 (Passing)
    • 5. 0: 65-74 (Failure)
    • Inc.: Incomplete
    • W: Withdrawn
    • D: Dropped

Chapter 1: The Foundation of Virology

Uriah’s Credo
  • Intrinsic Simplicity of Nature: Focus on simple, overall patterns rather than analyzing patchworks.
  • Originally stated by Salvador Luria in General Virology.
  • Highlights the importance of discovering unifying principles in science.
  • Remains relevant despite advancements in biology.

Viruses Defined

  • Definition: Microscopic infectious agents that can only reproduce inside infected cells.
  • Obligate parasites dependent on host cells for replication.
Structure and Spread
  • Spread via infectious particles called virions.
  • Virions contain RNA or DNA genomes surrounded by a protective protein coat.
Viral Replication Process
  • Viral genome directs the synthesis of viral components using host cell systems.
  • Progeny virus particles are formed through de novo self-assembly from newly synthesized components.
Advances in Virology
  • Improved understanding of virus particle structure and replication mechanisms.
  • More accurate definitions of viruses as unique agents.
Importance of Viruses
  • Historically recognized as pathogenic agents causing disease.
  • Studying viruses is important for reasons beyond their role in disease.

Why Study Viruses?

  • Viruses are everywhere in our environment.
  • They can cause major diseases but also have beneficial effects.
  • Studying viruses helps us understand biology, immunity, and evolution.

Viruses Are Everywhere

  • Viruses exist in air, water, and within organisms.
  • They infect humans, animals, plants, and even bacteria.
  • Billions of virus particles are encountered daily.

Viruses Infect All Living Things

  • Viruses infect a broad range of hosts:
    • Humans, animals, plants
    • Microbes (bacteria, fungi, algae)
    • Other viruses
  • Viral infections in agriculture impact global economy and food supply.

Viruses and Human Disease

  • While many viruses do not harm us, some cause severe diseases.
  • Examples:
    • Smallpox, Influenza, HIV/AIDS
    • Respiratory and gastrointestinal infections
    • Viral-induced cancers (~20% of human cancer cases)

Beneficial Viruses

  • Viruses play key roles in ecosystems:
    • Marine viruses sustain oceanic food chains.
    • Some viruses protect against bacterial infections.
    • Endogenous retroviruses are essential for placental development.

Cross-Species Transmission

  • Viruses can jump species barriers (zoonotic transmission).
  • Examples:
    • HIV (from primates)
    • Ebola and SARS (from wildlife)
    • Avian Influenza H5N1 (from birds to humans)
  • Human activity increases these risks.

Viruses in Human DNA

  • 5-8% of human DNA consists of viral sequences.
  • Some viral genes are beneficial and have been retained through evolution.
  • Viral DNA helps us understand evolutionary history.

Viruses as Tools for Scientific Discovery

  • Studies on viruses have advanced our knowledge of biology.
  • Examples:
    • Bacteriophages led to modern molecular biology.
    • Cancer research was revolutionized by studying viruses.
    • Viruses are used in gene therapy and vaccine development.

Historical Impact of Viruses

  • Viruses have affected human history:
    • Ancient records of rabies, smallpox, and polio.
    • Epidemics shaped civilizations (e.g., smallpox in the Americas).
    • Viral diseases continue to impact global health.

The First Vaccines

  • Variolation: Early smallpox prevention method.
  • Edward Jenner (1796): Developed the first vaccine using cowpox.
  • Louis Pasteur: Developed vaccines for rabies and yellow fever.

Microorganisms as Pathogenic Agents

  • Microorganisms play a crucial role in disease causation.
  • 19th-century scientific advancements led to major discoveries in microbiology.
  • From bacterial pathogens to viruses, our understanding of diseases evolved significantly.

Early Discoveries of Microorganisms

  • Antony van Leeuwenhoek (1632–1723): First to observe microscopic life (wee animalcules).
  • Microscopic organisms include protozoa, algae, and bacteria.
  • Early theories included spontaneous generation, later disproved by Louis Pasteur.

Germ Theory and Disease Causation

  • Before germ theory, diseases were attributed to miasma (bad air).
  • Louis Pasteur’s Experiments: Disproved spontaneous generation.
  • Robert Koch’s Postulates (1890): Criteria for linking microbes to disease:
    *Microbe must be found in diseased hosts.
    *Microbe must be isolated and grown in culture.
    *Pure culture must cause disease in a healthy host.
    *Microbe must be re-isolated from the newly infected host.

The Discovery of Viruses

  • 1892: Dmitri Ivanovsky – Filterable agent causing tobacco mosaic disease.
  • 1898: Martinus Beijerinck – Coined contagium vivum fluidum.
  • Friedrich Loeffler & Paul Frosch – Identified viruses in foot-and-mouth disease.
  • Viruses differ from bacteria – require a host cell to replicate.

Early Virus Research and Bacteriophages

  • Frederick Twort (1915) & Félix d’Hérelle (1917) – Discovery of bacteriophages.
  • 1935: Wendell Stanley crystallized Tobacco Mosaic Virus (TMV).
  • Electron microscopy revealed viral structures.

Key Properties of Viruses

  • Smaller than bacteria.
  • Obligate intracellular parasites.
  • Require host cells to reproduce.
  • Do not grow and divide like bacteria.
  • Examples: Influenza, HIV, Poliovirus.

The Role of Bacteriophages in Molecular Biology

  • Phages helped prove DNA is genetic material.
  • 1952: Hershey-Chase experiment used radioactive labeling.
  • DNA, not proteins, carries genetic instructions.

Cell Culture and Modern Virology

  • 1949: John Enders cultured poliovirus in human cells.
  • Development of HeLa cells and immortalized cell lines.
  • Enabled vaccine production (Polio, Measles, COVID-19).

Simpler Infectious Agents

  • Viroids: Infectious RNA molecules affecting plants.
  • Prions: Infectious proteins causing neurodegenerative diseases.
  • Satellites: Require a helper virus for replication (e.g., hepatitis delta virus).

Virus Classification: The Debate

  • Early controversies in classification methods.
  • Virus diversity led to differing opinions on taxonomy.
  • Two major perspectives:
    • No clear evolutionary relationships between viruses.
    • Grouping by shared properties offers practical advantages.

The Classical Virus Classification System

  • Proposed by Lwoff, Horne, and Tournier (1962).
  • Grouped viruses based on shared properties rather than host type.
  • Key classification criteria:
    • Nucleic acid type (DNA or RNA).
    • Capsid symmetry (icosahedral, helical, complex).
    • Presence or absence of an envelope.
    • Virion and capsid dimensions.

Modern Molecular Classification of Viruses

  • Genome sequencing revolutionized classification.
  • Example: Hepatitis C virus classified as Flaviviridae based on genome sequence.
  • Some viruses with distinct genomes share replication mechanisms:
    • Retroviridae, Hepadnaviridae, and plant viruses share reverse transcription.
    • NCLDVs (nucleocytoplasmic large DNA viruses): Includes Mimiviridae, Pandoraviridae, and Poxviridae.

The ICTV Virus Taxonomy

  • International Committee on Taxonomy of Viruses (ICTV) continues to manage virus classification.
  • 2024 ICTV Report: 12,869 virus species classified.
  • 2,803 genera, 505 families, and 47 orders.
  • 2,884 species names updated to binomial format (genus + species epithet).
  • Includes unclassified viruses, satellites, viroids, and prions.
  • Metagenomics continues to reveal vast viral diversity, with many uncharacterized species.

The Baltimore Classification System

  • Developed by David Baltimore based on genome structure and replication strategy.
  • Categorizes viruses into seven genome types:
    • dsDNA viruses
    • ssDNA viruses
    • dsRNA viruses
    • (+) ssRNA viruses
    • (-) ssRNA viruses
    • RNA reverse-transcribing viruses
    • DNA reverse-transcribing viruses
  • Provides insight into mRNA synthesis pathways.

The Central Dogma and Viral Replication

  • Francis Crick’s central dogma: DNA→RNA→ProteinDNA \rightarrow RNA \rightarrow Protein
  • Viruses must generate mRNA for host translation.
  • Baltimore classification predicts viral replication steps.

Key Steps in Viral Propagation

  • Common viral strategies for infection and replication:
    • Attachment to host cell receptors.
    • Entry via membrane fusion or endocytosis.
    • Decoding of genome to express viral proteins.
    • Genome replication using host or viral enzymes.
    • Assembly and release of new virions.
  • Successful viruses establish long-term host presence.

The Expanding Viral Universe

  • Metagenomics has transformed virology:
    • 93% of sequences in some studies lack known homologs.
    • Giant viruses challenge traditional virus definitions.
    • Unexplored viral diversity remains vast.
  • Future research will continue to uncover new viral mechanisms.