Microbiology Lecture Notes: Chapter 5 - Viruses and Subviral Agents

Course Logistics and Schedule Adjustments

• General Disclaimer and Attendance Policy: The instructor noted that while students from previous courses (Pathology) know they often stay late, this specific course usually only extends late for specific weeks (e.g., last week and this week).
• Chapter Coverage and Syllabus Changes:
  • The instructor exerts flexibility over the syllabus based on the "subject to change" asterisk.
  • Several chapters are often skipped to make the time spent in class worthwhile (avoiding long commutes for five-minute lessons).
  • Chapters typically skipped in Patho included Chapter 3, 22, 23, 24, and everything after Chapter 26.
  • For the current course, Chapter 8 is the only one explicitly cut.
  • Most weeks will cover two chapters, except for one week after the midterm which may cover three chapters (potentially weeks 7, 8, or 9).
• Topic Approvals: The instructor clarified the process for approving research or project topics. If the instructor initialed and dated the signup sheet, the student is approved. There was a brief discussion about students passing the sheet around without proper instructor sign-off, meaning some students are not yet ready to proceed.

Questions & Discussion: Course Administration

• Student Question: "How thick is your book?"
• Instructor Response: The instructor alluded to the volume of material remaining, including nervous system and gastrointestinal (GI) chapters, and confirmed that quizzes would be likely given the volume of chapters (four chapters at a point).
• Student Question: "How did you—you didn't approve nobody?"
• Instructor Response: "When you signed it, and I put my initial and date next to it. Yeah… You guys kinda did not listen to me and pass it around the room… then you're not doing good right yet."
• Student Suggestion: "Oh, you could've just told us to stay home that day [for short chapters]."
• Instructor Response: The instructor explained that they restructure the algorithm to combine short chapters so students have a lecture long enough to justify the commute from places like NYC.

General Viral Structure and Characteristics

• Definition: Viruses are microscopic particles that affect cells. They are not considered organisms and are classified as non-living.
• Obligate Intracellular Parasites: They cannot reproduce on their own. They require a host cell to duplicate their genetic material and use the host's machinery for replication.
• Size: They are extremely small, even smaller than most bacteria. This allows them to infect bacteria (prokaryotes) as well as eukaryotes.
• Genetic Composition: Every virus contains some form of nucleic acid, either DNA or RNA.
• Clinical Relevance: Because they are non-living, antibiotics are ineffective. Treatment is generally symptomatic. Specific antivirals exist that attack the virus at specific stages of its life cycle (discussed further in Pharmacology).

Viral Taxonomy and Classification Systems

• Difficulty of Classification: Categorizing viruses is difficult because they are non-living particles rather than living organisms.
• Classification Criteria: The International Committee on Taxonomy of Viruses (ICTV) classifies viruses based on:
  • Shape/Morphology.
  • Type of nucleic acid.
  • Replication method (e.g., lysis vs. budding).
  • Host organisms affected.
  • Types of diseases caused.
• Naming Conventions:
  • Order: Ends in -virales.
  • Family: Ends in -viridae.
  • Subfamily: Ends in -virinae.
  • Genus/Species: Ends in -virus (e.g., Adenovirus, Rotavirus).

Baltimore Classification System

This system organizes viruses into seven groups based on the relationship between the viral genome and the messenger RNA ($mRNA$) they produce.

• Group DNA vs. RNA:
  • DNA-based: Groups $1$, $2$, and $7$.
  • RNA-based: Groups $3$, $4$, $5$, and $6$.
• Strandedness:
  • Group 1: Double-stranded ($DS$) DNA.
  • Group 2: Single-stranded ($SS$) DNA.
  • Group 3: Double-stranded ($DS$) RNA.
  • Group 4: Single-stranded ($SS$) RNA.
  • Group 5: Single-stranded ($SS$) RNA.
  • Group 6: Single-stranded ($SS$) RNA.
  • Group 7: Double-stranded ($DS$) DNA.

Viral Morphology and Components

• Size Range: They range from very small to relatively large (for a virus). Most are invisible under light microscopy, with the exception of the Mimivirus discovered in $2003$.
• Capsid: A protein coat that protects the genetic material. It is composed of protein subunits called capsomeres, which are themselves made of protomers.
  • Hierarchy: Protomers $\rightarrow$ Capsomeres $\rightarrow$ Capsid.
• Nucleocapsid: The complex formed by the interaction between nucleic acids and viral capsid proteins.
• Nucleoproteins: Proteins associated specifically with the nucleic acids.
• Spikes: Long projections from the nucleocapsid that act as receptors to interact with and land on host cells.
• Virion: A fully assembled, functional, infectious virus particle outside of a host cell.
• Envelope: A membrane surrounding the capsid. Viruses without this are termed "naked."

Morphological Shapes of Viruses

• Helical Viruses: These have rod-shaped capsomeres that form a hollow tube (like a poster tube). The single-stranded RNA or DNA is coiled inside. They can be naked or enveloped.
• Icosahedral Viruses: These are 3D geometric figures containing:
  • $12$ corners.
  • $20$ triangular faces.
  • $30$ edges.
  • Examples include families like Herpesviridae, Adenoviridae, Papovaviridae, and Parvoviridae.
• Complex Viruses:
  • Bacteriophage: Resembles a "spacer" or "nanobot." It has a head (capsid containing nucleic acid) and a tail consisting of a hollow contractile sheath and a needle. It lands on a host, the sheath contracts, and the needle injects the genetic code.
  • Pox Virus: Lacks a regular capsid; instead, it has a nucleoid surrounded by a membrane and two lateral bodies that occupy space.

The Mechanics of Envelopes and Budding

• Source of Envelope: Obtained through budding, where the virus pushes through the host cell's plasma membrane or endoplasmic reticulum ($ER$).
• Biochemical Composition: The envelope is composed of a phospholipid bilayer from the host.
  • Phospholipid Structure: Consists of a hydrophilic head and hydrophobic tails. When the virus buds out, the membrane pinches off and encloses the virus so the hydrophobic tails are not exposed to the fluid environment.
• Protein Replacement: Effectively, host membrane proteins are eventually replaced by viral glycoproteins.

Genomic Variations

• Nucleic Acid Types: Can be linear or a closed loop (circular).
• Standard Rule: Most viruses contain either DNA or RNA, not both.
• Exception: Specific mention of the Cytomegalovirus, which is a DNA virus that contains fragments of RNA.
• Polymerase Requirements:
  • DNA Viruses: Depend on DNA-dependent DNA polymerase for replication.
  • RNA Viruses: Must provide their own polymerase for transcription.
  • Reverse Transcribing Viruses: (Groups $6$ and $7$) Use RNA genomes but replicate via a DNA intermediate, essentially performing transcription backwards (RNA to DNA) to integrate with host DNA.

Bacteriophage Multiplication Cycle

1. Adsorption: The phage adheres to the bacterial surface using tail fibers that connect to specific phage receptors (on the cell wall, pili, or flagella).
2. Penetration: The contractile sheath contracts, and the needle injects the DNA/RNA into the host. The protein structure remains outside.
3. Replication: The viral nucleic acid takes over the host machinery.
   • Eclipse Period: A phase where no infectious phage particles are yet found in the host cell because parts are being made but not assembled.
   • Intercellular Accumulation Phase: Viral parts accumulate in the cell.
4. Assembly: The various viral components are put together.
5. Maturation: The DNA/RNA is packaged into the capsid, creating a full virion.
6. Release: Occurs through Lysis, where the host cell wall is destroyed (explodes) due to the volume of produced viruses, allowing them to float away and infect new cells.

Lysogenic vs. Lytic Cycles

• Lysogenic (Temperate) Phages: The phage DNA becomes a prophage. It is integrated into the host's chromosome and passed to daughter cells through binary fission without immediately destroying the host.
• Induction: Eventually, the prophage may exit the chromosome and enter the lytic cycle, leading to lysis.

Animal Virus Multiplication

Animal virus replication follows similar steps to bacteriophages but with a key difference:

• Adsorption: Virus attaches to host receptors. If a cell lacks the receptor, it is resistant (e.g., Opossums are resistant to Rabies).
• Penetration: Host cells often pull the virus in via pinocytosis.
• Uncoating: An extra step where the envelope and capsid are removed by host digestive enzymes to release the viral nucleic acid into the cytoplasm.
• Replication/Assembly/Release: Similar to phages, though release can be via lysis (non-enveloped) or budding (enveloped).

Types of Viral Infections and Effects

• Abortive Infections: Infection occurs, but the virus is destroyed before it can replicate.
• Lytic (Cytocidal) Infections: Leads to host cell death via lysis.
• Persistent Infections:
  • Chronic: Continuous viral production without immediate cell death.
  • Latent: Limited or no synthesis; the virus hides in cells (e.g., Herpes).
  • Slow: Long incubation periods (taking years for disease to manifest).
• Transforming Infections: Lead to oncogenic (cancerous) changes (e.g., Hepatitis C, HPV).

Host Cell Damage (Cytopathic Effects)

• Morphological Effects: Altered cell shape, detachment from tissue, membrane fusion, membrane permeability changes, and inclusion bodies.
• Functional Changes: Altered ion/electrolyte movement and cellular activities.
• Biochemical Effects: Inhibition or alteration of the host cell's four major macromolecules: Lipids, Proteins, Carbohydrates, and Nucleic Acids.
• Genotoxic Effects: Direct damage to host DNA, leading to mutations and cancer.

Major Viral Families and Associated Diseases

DNA Viruses

• Adenoviruses: $57$ types; stable against physical/chemical agents; causes respiratory, GI, eye, bladder, and skin issues. Used in gene therapy.
• Hepadnaviruses: Hepatitis B.
• Herpesviruses: Type $1$, Type $2$, and Chickenpox.
• Papilloma and Polyomaviruses: Warts (plantar, flat, digitating) and cervical carcinoma (HPV).
• Parvoviruses: Only one human strain, B19.
• Pox Viruses: Largest viruses; includes Smallpox.

RNA Viruses

• Coronaviruses: A family causing respiratory and enteric diseases (COVID-19, SARS).
• Orthomyxoviruses: Influenza strains A, B, and C.
• Paramyxoviruses: Hantavirus or Nipah virus (Note: Hantavirus is later associated with Bunyaviridae via rodent excreta).
• Picornaviruses: Large family of "itty bitty" viruses; includes Rhinovirus and Enterovirus.
• Rhabdoviruses: Rabies; affects plants, insects, fish, and mammals.
• Reoviruses: Includes Rotavirus, causing $30\%$ of child diarrhea hospitalizations.
• Retroviruses: HIV.
• Togaviruses: Rubella.
• Flaviviruses: Yellow Fever, West Nile, Dengue, Hepatitis C.

Subviral Agents and Prions

• Viroids: Plant-based viruses that do not need helper viruses.
• Virusoids: Require a helper virus to cause infection.
  • Example: Hepatitis D is a virusoid that requires Hepatitis B to function; D amplifies the severity of B.
• Prions: Proteinaceous infectious particles.
  • They are abnormally folded proteins that lack nucleic acids.
  • They cause Transmissible Spongiform Encephalopathies (TSE).
  • Examples: Mad Cow Disease, Creutzfeldt-Jakob Disease, and Kuru (transmitted via cannibalism, discussed in the GI system).