Viruses and Prions: Structure, Replication, and Pathogenesis

Microbiology Chapter 6 – Viruses and Prions

Viruses as Nonliving Microbes

Viruses are classified as nonliving microbes because they lack cellular structure and cannot reproduce independently. They require host cells to replicate and do not carry out metabolic processes on their own.

• Noncellular: Viruses are not made of cells.

• Replication: Viruses use host cell machinery to reproduce.

• Obligate Intracellular Pathogens: Viruses must invade living cells to multiply.

Comparison: Viruses vs. Prokaryotic and Eukaryotic Cells

The following table summarizes key differences among viruses, prokaryotes, and eukaryotes.

Characteristic	Viruses	Prokaryotes	Eukaryotes
Cell?	No	Yes	Yes
Considered alive?	No	Yes	Yes
Relative size	Generally smaller than prokaryotes and eukaryotes	Most are larger than viruses, smaller than eukaryotes	Usually larger than prokaryotes and viruses
Plasma membrane	No	Yes	Yes
Genetic material	DNA or RNA	DNA	DNA
Metabolism	No	Yes	Yes
Replication	Host cell machinery	Binary fission	Mitosis/meiosis

Viral Structure: Capsids, Envelopes, and Spikes

Viruses have distinct structural components that aid in their infectivity and classification.

• Capsid: Protein coat surrounding the viral genome, built from subunits called capsomeres.

• Capsid Shapes:

  • Helical: Rod-like, e.g., coronavirus SARS CoV-2

  • Icosahedral: Spherical, e.g., adenovirus

  • Complex: e.g., bacteriophage

• Envelope: Lipid membrane derived from host cell, found in many animal viruses.

• Spikes: Glycoprotein extensions for host cell attachment and entry.

Function: Protect viral genome, aid in attachment and penetration into host cells.

Viral Genomes: DNA and RNA Viruses

Viruses use their genomes to direct the production of proteins necessary for replication.

• DNA Viruses: Use host cell machinery for transcription and translation.

• RNA Viruses: May require viral RNA-dependent RNA polymerase for replication.

Single-stranded antisense RNA viruses must transcribe their genome into readable mRNA before translation.

• $\text{RNA-dependent RNA polymerase (RdRp)}$ builds RNA from existing RNA templates.

Retroviruses: Use reverse transcriptase to convert RNA into DNA, which integrates into the host genome.

Genomic Variation and Evolution in Viruses

Viral genomes can mutate rapidly, especially in RNA viruses, leading to genetic diversity and evolution.

• Genetic Drift: Minor mutations accumulate over time.

• Genetic Shift: Major changes, often due to recombination or reassortment.

• Antigenic Drift: Small changes in viral proteins, e.g., influenza HA and NA spikes.

• Antigenic Shift: Large changes, potentially leading to new viral strains.

Consequence: New strains may evade host immunity, complicating vaccine development.

Classification of Viruses

Viruses are classified based on several properties:

• Type of nucleic acid (DNA or RNA)

• Capsid symmetry (helical, icosahedral, complex)

• Presence or absence of envelope

• Genome architecture (ssDNA, dsDNA, ssRNA, etc.)

Medically Important Viral Families

Many viral families are significant in human medicine, including:

• Herpesviridae: Herpes simplex viruses

• Orthomyxoviridae: Influenza viruses

• Retroviridae: HIV

• Picornaviridae: Poliovirus, rhinovirus

Virus Host Range and Tropism

Host range refers to the spectrum of hosts a virus can infect, while tropism describes the specificity for certain cell types.

• Example: Influenza infects both humans and pigs, but avian strains may not infect humans.

• Tropism: Determined by viral surface proteins binding to specific host cell receptors.

Naming Conventions for Viruses

Viruses are named using a hierarchical taxonomy. The following table summarizes the conventions:

Taxon	Examples	Notes
Order	Herpesvirales	Ends with -virales
Family	Herpesviridae	Ends with -viridae
Subfamily	Alphaherpesvirinae	Ends with -virinae
Genus	Simplexvirus	Ends with -virus
Species	Human herpesvirus 1	Descriptive name
Common Name	Herpes simplex virus 1	Often used in clinical context

Bacteriophage Replication: Lytic and Lysogenic Cycles

Bacteriophages can replicate via two main cycles:

• Lytic Cycle: Virus replicates and lyses the host cell, releasing new phages.

• Lysogenic Cycle: Viral genome integrates into host DNA and replicates with the cell.

Steps in Lytic Replication:

1. Attachment

2. Penetration

3. Replication

4. Assembly

5. Release

Generalized Steps for Animal Virus Replication

Animal viruses follow a series of steps to infect host cells:

1. Attachment: Virus binds to host cell receptors.

2. Penetration: Entry via fusion or endocytosis.

3. Uncoating: Viral genome released.

4. Replication: Genome copied and proteins synthesized.

5. Assembly: New virions assembled.

6. Release: Virions exit the cell (lysis or budding).

Enveloped vs. Naked Animal Viruses

Enveloped and naked viruses differ in their release mechanisms:

• Enveloped Viruses: Bud from host cell, taking a portion of the plasma membrane.

• Naked Viruses: Lyse the host cell during release, often killing the cell.

Chronic and Latent Viral Infections

Viruses can cause persistent infections:

• Chronic Infection: Virus replicates slowly, symptoms may be mild or absent.

• Latent Infection: Virus remains dormant, can reactivate later.

Examples: HIV (chronic), Herpes simplex virus (latent)

Oncogenic Viruses and Cancer

Some viruses can cause cancer by disrupting normal cell regulation.

Virus	Genome Type	Oncogenic?	Cancer Link	Cancer-Causing Mechanism
Human papillomavirus (HPV)	DNA	Yes	Cervical, anal, oropharyngeal	Viral genes disrupt cell cycle regulation
Epstein-Barr virus (EBV)	DNA	Yes	Burkitt's lymphoma, nasopharyngeal carcinoma	Latent infection, cell transformation
Hepatitis B virus	DNA	Yes	Liver cancer	Chronic infection, integration into host genome
Hepatitis C virus	RNA	Yes	Liver cancer	Chronic infection, inflammation

Methods for Growing Bacteriophages and Animal Viruses

Viruses require host cells for propagation:

• Bacteriophages: Grown in bacterial cultures (liquid broth, agar plates).

• Animal Viruses: Grown in cell cultures, embryonated eggs, or animal models.

Plaque Assay

Plaque assays are used to quantify viruses by counting clear zones (plaques) formed on host cell layers.

• Useful for: Determining viral concentration and infectivity.

Methods for Detecting Viral Proteins and Genetic Material

• Agglutination Tests: Detect viral antigens using specific antibodies.

• ELISA: Enzyme-linked immunosorbent assay for protein detection.

• Immunofluorescence: Uses fluorescent antibodies to detect viral proteins.

• PCR: Polymerase chain reaction for amplifying viral nucleic acids.

Advantages: High sensitivity and specificity. Limitations: May require specialized equipment and expertise.

Antiviral Drug Approaches

Antiviral drugs target various stages of the viral life cycle:

• Entry Inhibitors: Block virus from entering host cells.

• Reverse Transcriptase Inhibitors: Prevent viral genome replication (e.g., HIV).

• Nucleoside Analogues: Interfere with viral DNA/RNA synthesis.

Examples: Acyclovir (herpes), Oseltamivir (influenza), AZT (HIV)

Prions and Prion Diseases

Prions are infectious proteins that cause neurodegenerative diseases by inducing abnormal folding of normal proteins.

• Diseases: Creutzfeldt-Jakob disease (CJD), Kuru, fatal familial insomnia

• Symptoms: Progressive neurological decline, "spongy brain" appearance

Transmission of Creutzfeldt-Jakob Disease (CJD)

• Consumption of contaminated meat

• Use of contaminated surgical instruments

• Transplantation of infected tissues

Prion-like Neurological Disorders

Neurological disorders such as Alzheimer's, Parkinson's, and ALS may involve prion-like mechanisms, where misfolded proteins propagate disease by altering normal protein conformation.

• Mechanism: Misfolded proteins induce similar misfolding in normal proteins, leading to disease progression.