Horizontal Gene Transfer, Viruses, and Prions: Key Concepts in Microbial Genetics and Infectious Disease

Horizontal Gene Transfer (HGT) in Bacteria

3 Main Processes of HGT

Horizontal gene transfer allows bacteria to acquire genetic material from other organisms, contributing to genetic diversity and the spread of traits such as antibiotic resistance.

• Transformation: Uptake of naked DNA fragments from the environment by a bacterial cell.

• Transduction: Transfer of DNA from one bacterium to another via a bacteriophage (virus that infects bacteria).

• Conjugation: Direct transfer of DNA (usually a plasmid) between two bacterial cells through a pilus (sex pilus).

Similarities

• All three involve gene transfer between different bacterial cells (not parent-to-offspring).

• Each can lead to genetic variation in bacteria.

• All can spread antibiotic resistance genes or virulence factors.

• Require donor and recipient bacteria.

Differences

Process	Method of DNA Transfer	Requires Cell-to-Cell Contact?	Mediated by Phage?	Type of DNA Transferred
Transformation	Uptake of DNA from environment	No	No	Small fragments of chromosomal DNA
Transduction	DNA transferred by bacteriophage	No	Yes	Chromosomal or plasmid DNA
Conjugation	Direct plasmid transfer	Yes	No	Usually plasmid (e.g., F plasmid, R plasmid)

Generalized vs. Specialized Transduction

• Generalized Transduction: Occurs during the lytic cycle of a bacteriophage. Any random fragment of bacterial DNA can be accidentally packaged into a new phage head and transferred to another bacterium.

• Specialized Transduction: Occurs during the lysogenic cycle of a temperate phage. Only specific genes located near the prophage insertion site are transferred when the prophage excises incorrectly.

Effects of HGT on Human Health

• Spread of Antibiotic Resistance: HGT can transfer resistance genes between bacteria, leading to multidrug-resistant strains (e.g., MRSA, VRE).

• Emergence of New Pathogens: Bacteria can acquire toxin genes or other virulence factors, resulting in new pathogenic strains.

• Transfer of Malleable Traits: HGT enables adaptation to new environments or hosts.

Viruses, Viroids, and Prions

Definitions and Key Features

• Virus: Obligate intracellular parasite with DNA or RNA genome, surrounded by a protein coat (capsid). May have an envelope derived from host cell membrane.

• Viroid: Small, circular, single-stranded RNA molecules that infect plants. Lack a protein coat and do not encode proteins.

• Prion: Infectious protein particles that lack nucleic acids. Cause neurodegenerative diseases by inducing misfolding of normal proteins.

Virus Structure

• Virion: Complete virus particle outside a host cell.

• Capsid: Protein shell surrounding the nucleic acid.

• Envelope: Lipid bilayer derived from host cell, present in some viruses (enveloped viruses).

Envelope vs. Non-enveloped Viruses

• Enveloped viruses: Have a lipid bilayer and proteins from the host cell; more sensitive to environmental conditions.

• Non-enveloped (naked) viruses: Lack an envelope; more resistant to desiccation and disinfectants.

Nucleic Acid Types in Viruses

• Double-stranded DNA (dsDNA): Common in many viruses (e.g., herpesviruses).

• Single-stranded DNA (ssDNA): Rare, but present in some viruses.

• Double-stranded RNA (dsRNA): Uncommon, but found in some viruses.

• Single-stranded RNA (ssRNA): Can be positive-sense (+ssRNA) or negative-sense (−ssRNA).

Viral Replication Cycles

Lytic Replication Cycle (for animal viruses)

• Attachment: Virion attaches to host cell.

• Entry/Penetration: Virion or genome enters host cell.

• Synthesis: Host cell machinery synthesizes viral nucleic acids and proteins.

• Assembly: New virions are assembled in the host cell.

• Release: New virions are released, often killing the host cell.

Animal Virus Replication Steps

• Attachment

• Entry (penetration, membrane fusion, endocytosis)

• Uncoating (release of viral genome)

• Synthesis

• Assembly

• Release

Bacteriophage Replication: Lytic vs. Lysogenic Cycles

• Lytic Cycle: Phage replicates and lyses (kills) the host cell.

• Lysogenic Cycle: Phage DNA integrates into host genome as a prophage, replicates with host cell, and can later enter the lytic cycle.

Key Differences

• Lytic cycle is always productive and kills the host cell.

• Lysogenic cycle can be latent, with the phage genome integrated and replicated with the host without killing it.

Transduction: Generalized vs. Specialized

Feature	Generalized Transduction	Specialized Transduction
Cycle involved	Lytic	Lysogenic → Lytic
DNA packaging error	Random	Specific (adjacent to prophage)
Genes transferred	Any random gene from donor	Only specific genes near prophage
Example	Random gene from E. coli	Galactose metabolism gene from E. coli

Latency and Proviruses

• Latency: Virus remains inactive within a host cell for extended periods (years or decades).

• Provirus: Viral genome integrated into host chromosome; can be permanent and inherited by daughter cells.

Viruses and Cancer

• About 20-25% of human cancers are associated with viruses.

• Examples: Burkitt's lymphoma, Hodgkin's disease, Kapos's sarcoma, Cervical cancer.

• Mechanisms: Viral integration can disrupt normal cell cycle regulation, leading to uncontrolled cell division (neoplasia).

Retroviruses

• RNA viruses that use reverse transcriptase to synthesize DNA from their RNA genome.

• DNA integrates into host genome as a provirus.

• Example: Human immunodeficiency virus (HIV).

Viroids and Prions

Viroids

• Circular, single-stranded RNA molecules.

• Infect plants; do not encode proteins.

• Cause stunted growth and other plant diseases.

Prions

• Infectious proteins that cause neurodegenerative diseases.

• Composed solely of protein; lack nucleic acids.

• Cause misfolding of normal proteins, leading to brain damage and spongiform degeneration.

• Extremely resistant to heat, radiation, and disinfectants.

Prion Diseases: Examples and Features

Feature	Bovine Spongiform Encephalopathy (BSE)	Creutzfeldt–Jakob Disease (CJD)
Host	Cattle	Humans
Cause	Misfolded PrPSc from contaminated feed	Misfolded PrPSc (spontaneous or from contaminated medical tissue)
Transmission	Ingestion of infected tissue	Sporadic, inherited, or via consumption of infected beef
Major Symptoms	Behavior changes, loss of coordination, paralysis	Dementia, ataxia, muscle stiffness, rapid mental decline
Outcome	Fatal neurodegeneration	Fatal neurodegeneration
Zoonotic Link	Yes — can cause vCJD in humans	vCJD form traced to BSE exposure

Summary

• Horizontal gene transfer, viruses, viroids, and prions are central to microbial genetics and infectious disease.

• Understanding these processes is essential for controlling the spread of antibiotic resistance and emerging pathogens.