Viruses and Prions: Structure, Replication, and Pathogenesis

Viruses and Prions

Main Differences Between Viruses, Bacteria, and Prions

Viruses, bacteria, and prions are all infectious agents, but they differ significantly in structure, replication, and pathogenic mechanisms.

• Bacteria: Prokaryotic, cellular organisms that reproduce by binary fission, possess both DNA and RNA, have ribosomes, and generate ATP through metabolism.

• Viruses: Acellular entities composed of nucleic acid (DNA or RNA) surrounded by a protein coat (capsid), sometimes with a lipid envelope. They are obligate intracellular parasites and lack ribosomes and ATP-generating metabolism.

• Prions: Infectious proteins lacking nucleic acids. They cause disease by inducing abnormal folding of specific normal cellular proteins.

Intracellular Pathogen: An organism or agent that must invade and replicate within a host cell to survive and reproduce.

Obligate Intracellular Pathogen: An organism or agent that cannot reproduce outside the host cell (e.g., viruses, some bacteria like Chlamydia and Rickettsia).

Comparison Table: Bacteria, Viruses, and Prions

Feature	Typical Bacteria	Intracellular Bacteria (Rickettsias/Chlamydias)	Viruses	Prions
Intracellular Parasite/Pathogen	No	Yes	Yes	No
Plasma Membrane	Yes	Yes	No	No
Binary Fission	Yes	Yes	No	No
Pass through Bacteriological Filters	No	Yes	Yes	Yes
Possess Both DNA and RNA	Yes	Yes	No (one or the other)	No
ATP-Generating Metabolism	Yes	No	No	No
Ribosomes	Yes	Yes	No	No
Sensitivity to Antibiotics	Yes	Yes	No	No
Sensitivity to Antivirals	No	No	Yes	No
Sensitivity to Interferon	No	No	Yes	No

General Structure of a Virus

Virion Components

A virion is a complete, infectious virus particle. Its main components include:

• Capsid: Protein coat surrounding the viral nucleic acid.

• Nucleocapsid: The combination of the viral genome and the capsid.

• Envelope: (In enveloped viruses) A phospholipid membrane derived from the host cell, covering the nucleocapsid.

• Spikes: Glycoprotein projections from the envelope, involved in host cell recognition and attachment.

Types of Viruses

• Naked (Non-enveloped) Viruses: Consist only of a capsid and genome; lack an envelope. Viral attachment proteins are capsomeres.

• Enveloped Viruses: Possess a lipid envelope with embedded host and viral proteins, including glycoprotein spikes for host cell attachment.

Host Range: The spectrum of host cells a virus can infect, determined by specific interactions between viral attachment proteins and host cell receptors.

Viral Cell Tropism: The specificity of a virus for a particular host tissue, often determined by tissue-specific receptors.

Virion Structures

• Helical: Rod-shaped (e.g., Tobacco Mosaic Virus, TMV)

• Icosahedral: Spherical with 20 triangular faces (e.g., Human Papillomavirus, HPV)

• Complex: Complicated structures (e.g., Bacteriophage T4)

Virus Taxonomy

• Genus names: End in -virus

• Family names: End in -viridae

• Viral species: Group of viruses sharing genetic information and ecological niche

• Subspecies: Designated by numbers

Genetic Identity: Viruses of the same species have the highest percentage of genetic identity.

Growing Viruses in the Laboratory

Viral Plaques and Plaque Forming Units (pfu)

• Viral Plaques: Clear zones on a cell lawn (e.g., E. coli) where viruses have lysed host cells.

• Plaque Forming Units (pfu): Quantitative measure of infectious virus particles.

Cytopathic Effect (CPE): Observable morphological changes in host cells due to viral infection, such as cell rounding, detachment, or death.

Primary Cell Lines: Cultures derived directly from animal tissues; have a limited lifespan.

Continuous Cell Lines: Immortalized cells that can be maintained indefinitely in culture.

Example: The image above shows bovine spleen cells (BSCs): normal cells (left) and cells with cytopathic effect after Parapoxvirus infection (right). Infected cells are rounded and detached, with increased empty spaces.

Viral Detection and Diagnosis

• Cytopathic Effects: Observed in cell cultures to indicate viral infection.

• Serological Tests: Detect immune response (e.g., Western blot, ELISA).

• Nucleic Acid Tests: Detect viral genome (e.g., RFLP, PCR, DNA sequencing).

Phases of Viral Replication and Growth

Viral Growth Curve

• Eclipse Phase: After viral entry, no extracellular virions are detectable; viral genome replication and protein synthesis occur.

• Maturation Phase: Assembly of new virions inside the host cell.

• Latent Period: Time during which the virus is not detectable outside the cell (includes eclipse and maturation phases).

Viral Replication Cycle

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

2. Penetration: Viral genome enters the host cell.

3. Synthesis: Replication of viral genome and synthesis of viral proteins.

4. Assembly: Packaging of viral genome into capsids.

5. Release: New virions exit the cell by lysis (cell destruction) or budding (enveloped viruses).

Bacteriophage Life Cycles

Bacteriophage T4 (Lytic/virulent)

• Attachment: Binds to LPS on Gram-negative bacteria.

• Entry: Tail fibers and lysozyme facilitate genome injection; lysozyme degrades peptidoglycan.

• Synthesis: Viral genome replication and protein synthesis, including lysozyme for release.

• Assembly: New virions assembled.

• Release: Host cell lysis, breaching both cytoplasmic membrane and peptidoglycan layer.

Temperate (Lysogenic) vs. Virulent (Lytic) Phages

• Lysogenic Cycle: Viral genome integrates into host DNA as a prophage, replicates with host, can later enter lytic cycle (induction).

• Lysogenic Conversion: Prophage genes alter host phenotype (e.g., Vibrio cholerae virulence).

• Main Difference: Lysogenic cycle involves integration and dormancy; lytic cycle results in immediate host cell lysis.

Animal Virus Infection

• Attachment: Viral proteins bind to tissue-specific host cell receptors (cell tropism).

• Entry: Naked viruses may inject DNA; enveloped viruses enter by endocytosis or membrane fusion.

• Synthesis: Uncoating of nucleocapsid; DNA viruses often replicate in nucleus, RNA viruses in cytoplasm.

• Outcomes:

  • Lytic infection (cell death)

  • Persistent infection

  • Latent infection (e.g., herpesviruses, HIV)

  • Transformation (tumor development, e.g., HPV)

• Assembly and Release: Enveloped viruses bud from the cell, acquiring host membrane.

Example: The image above shows (a) normal cervical cells and (b) cancerous cervical cells, illustrating transformation by viral infection (e.g., HPV).

Baltimore Classification of Viral Genomes

The Baltimore classification groups viruses based on their genome type and replication strategy. Each class uses specific enzymes for genome replication and mRNA synthesis.

Class	Genome Type	Genome Replicated By	mRNA Generated By
I	dsDNA	DNA polymerase	RNA polymerase
II	+ssDNA	-ssDNA (by DNApol), then RNA polymerase	RNA polymerase
III	dsRNA	RNA-dependent RNA polymerase (RdRp)	+ssRNA strand used as mRNA
IV	+ssRNA	RNA-dependent RNA polymerase	Genome used directly as mRNA
V	-ssRNA	+ssRNA (by RdRp), then used as mRNA	RNA-dependent RNA polymerase
VI	+ssRNA (retrovirus)	Reverse transcriptase to DNA, then RNA polymerase	DNA (by RT), then RNA polymerase
VII	dsDNA (with RNA intermediate)	RNA polymerase to RNA, then RT to dsDNA	RNA polymerase

Example: The image above summarizes the Baltimore classification, showing genome types, replication, and transcription strategies for each class.

Key Enzymes: DNA polymerase, RNA polymerase, RNA-dependent RNA polymerase, and reverse transcriptase are essential for viral genome replication and mRNA synthesis.

Latent and Persistent Viral Infections

• Latent Infection: Virus remains dormant within the host cell, with no active replication (e.g., herpes simplex virus).

• Persistent Infection: Virus continuously replicates at low levels without causing cell death (e.g., hepatitis B virus).

Prions – Proteinaceous Infectious Particles

• Genetic Material: Prions lack nucleic acids; they are composed solely of protein.

• Structure: Abnormally folded proteins that induce misfolding of normal host proteins.

• Diseases: Cause spongiform encephalopathies (e.g., Creutzfeldt-Jakob disease, mad cow disease).

• Replication: Prion proteins convert normal proteins into the prion form.

• Pathogenesis: Accumulation of prion proteins forms plaques in the CNS, leading to neuronal death and loss of function.