Viruses and Prions: Structure, Replication, and Pathogenesis

Chapter 6: Viruses and Prions

Introduction to Virology

Virology is the study of viruses, which are unique infectious agents distinct from prokaryotic and eukaryotic cells. This chapter explores the structure, classification, replication, and medical significance of viruses and prions.

Basic Features of Viruses

• Definition: Viruses are acellular infectious agents composed of genetic material (DNA or RNA) surrounded by a protein coat (capsid), and sometimes a lipid envelope.

• Key Features:

  • Obligate intracellular parasites: Require host cells for replication.

  • Lack cellular structures such as ribosomes and metabolic machinery.

  • Do not carry out metabolism independently.

Viruses as Nonliving Microbes

• Viruses are considered nonliving because they cannot reproduce or carry out metabolic processes outside a host cell.

• They do not respond to stimuli or maintain homeostasis.

Comparison: Viruses vs. Prokaryotic and Eukaryotic Cells

Viruses differ fundamentally from cells in structure and function.

Feature	Viruses	Prokaryotes	Eukaryotes
Cellular Structure	No	Yes	Yes
Genetic Material	DNA or RNA	DNA	DNA
Metabolism	No	Yes	Yes
Reproduction	Host-dependent	Binary fission	Mitosis/meiosis
Size	20–300 nm	0.5–5 μm	10–100 μm

Viral Structures: Capsids, Envelopes, and Spikes

• Capsid: Protein shell that encases the viral genome; composed of subunits called capsomeres.

• Envelope: Lipid membrane derived from the host cell, present in some viruses; contains viral proteins.

• Spikes: Glycoprotein projections from the capsid or envelope; facilitate attachment to host cells.

Genomic Varieties Among Viruses

• Viruses may have DNA or RNA genomes, which can be single-stranded (ss) or double-stranded (ds), linear or circular, and segmented or non-segmented.

• Examples:

  • dsDNA: Herpesviridae

  • ssDNA: Parvoviridae

  • ssRNA(+): Picornaviridae

  • ssRNA(-): Orthomyxoviridae

  • Retroviruses: HIV

Viral Genome Expression: DNA and RNA Viruses

• dsDNA and ssDNA Viruses:

  • dsDNA viruses use host machinery to transcribe mRNA from their DNA.

  • ssDNA viruses must first synthesize a complementary DNA strand to form dsDNA, then transcribe mRNA.

• ssRNA(+) Viruses: Genome acts directly as mRNA and is translated by host ribosomes.

• Retroviruses: Use reverse transcriptase to convert RNA genome into DNA, which integrates into the host genome and is transcribed to mRNA.

Viral Mutation and Evolution

• Mutations arise during viral genome replication, especially in RNA viruses due to lack of proofreading.

• RNA viruses evolve faster than DNA viruses, leading to rapid adaptation and emergence of new strains.

Antigenic Drift vs. Antigenic Shift

• Antigenic Drift: Gradual accumulation of mutations in viral genes, leading to minor changes in surface proteins.

• Antigenic Shift: Abrupt, major change due to reassortment of genome segments, resulting in new viral subtypes (notably in influenza viruses).

• Both processes contribute to influenza virus evolution and periodic outbreaks.

Host Range and Tropism

• Host Range: The spectrum of host species a virus can infect.

• Tropism: The specificity of a virus for a particular host tissue or cell type.

Bacteriophage Replication: Lytic and Lysogenic Cycles

• Lytic Cycle:

  1. Attachment

  2. Penetration

  3. Biosynthesis

  4. Assembly

  5. Release (host cell lysis)

• Lysogenic Cycle:

  1. Attachment and penetration

  2. Integration of phage DNA into host genome (prophage)

  3. Replication with host cell

  4. Induction into lytic cycle under certain conditions

Phage Conversion

• Occurs when a bacteriophage introduces new genes into a bacterial host, potentially altering its phenotype (e.g., toxin production).

• Medically important because it can increase bacterial virulence.

Animal Virus Replication Steps

1. Attachment: Virus binds to specific receptors on host cell.

2. Penetration: Entry of virus or genome into host cell.

3. Uncoating: Removal of capsid to release viral genome.

4. Replication: Synthesis of viral genomes and proteins.

5. Assembly: New virions are assembled from synthesized components.

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

Enveloped vs. Naked Virus Replication

• Enveloped Viruses: Typically enter by membrane fusion or endocytosis and exit by budding, acquiring an envelope from the host membrane.

• Naked Viruses: Usually enter by endocytosis and exit by host cell lysis.

Persistent Infections

• Persistent Infection: Virus remains in the host for long periods.

• Chronic Infection: Continuous, low-level viral production (e.g., hepatitis B).

• Latent Infection: Virus remains dormant, with periodic reactivation (e.g., herpes simplex virus).

Oncogenic Viruses

• Oncogenic Virus: A virus capable of causing cancer by disrupting normal cell cycle regulation.

• Examples:

  • Human papillomavirus (HPV) – cervical cancer

  • Epstein-Barr virus (EBV) – Burkitt lymphoma

  • Hepatitis B and C viruses – liver cancer

Prions: Structure and Pathogenesis

• Prion: Infectious protein particle lacking nucleic acid.

• Pathogenic prions are misfolded forms of normal proteins (PrPSc vs. PrPC).

• Prions induce misfolding of normal proteins, leading to disease.

Effects of Prion Diseases

• Prion diseases cause neurodegeneration, resulting in spongiform changes in brain tissue.

• Symptoms are progressive and fatal once they appear.

Prion Diseases in Animals

Species	Disease
Sheep	Scrapie
Cows	Bovine Spongiform Encephalopathy (BSE, "mad cow disease")
Deer/Elk	Chronic Wasting Disease

Prion Diseases in Humans

• Diseases:

  • Creutzfeldt-Jakob disease (CJD)

  • Variant CJD (vCJD)

  • Kuru

  • Fatal familial insomnia

• Transmission: Can occur via contaminated food, medical instruments, or inherited mutations.

Additional info:

• Vaccines and antiviral therapies are under development for emerging viruses (e.g., SARS-CoV-2).

• Understanding the virome (the collection of viruses in the human body) is an emerging field in microbiology.