Viruses, Viroids, and Prions

Viruses, Viroids, and Prions

General Characteristics of Viruses

  • Acellular pathogens

  • Obligatory intracellular parasites

  • Require living host cells to multiply

  • Contain either DNA or RNA

  • Have a protein coat

  • Do not possess ribosomes

  • Lack ATP-generating mechanisms

  • Absence of many genes necessary for reproduction, rely on host-cell genomes for replication

Comparison of Viruses and Bacteria

Key Differences:

Feature

Bacteria

Rickettsias

Chlamydias

Viruses

Intracellular Parasite

No

Yes

Yes

Yes

Plasma Membrane

Yes

Yes

Yes

No

Binary Fission

Yes

Yes

Yes

No

Pass Through Bacteriological Filters

No

No/Yes

Yes

Yes

Possess Both DNA and RNA

Yes

Yes

No

No

ATP-Generating Metabolism

Yes

Yes/No

No

No

Ribosomes

Yes

Yes

No

No

Sensitive to Antibiotics

Yes

Yes

No

No

Sensitive to Interferon

No

No

Yes

Yes

Host Range

  • Definition: The spectrum of host cells that a virus can infect.

  • Most viruses only infect specific types of cells within a single host.

  • Determined by:

    • Specific host attachment sites

    • Cellular factors

  • Bacteriophages: Viruses that infect bacteria

  • Size range: from 20 nm to 1000 nm in length

Viral Structure

  • Virion: A complete, fully developed viral particle.

  • Nucleic Acid: Can be DNA or RNA, single- or double-stranded; linear or circular.

  • Capsid: The protein coat made of capsomeres (subunits).

  • Envelope: A lipid, protein, and carbohydrate coating on some viruses.

  • Spikes: Projections from the outer surface that facilitate attachment and viral recognition.

General Morphology of Viruses

  • Based on capsid structure:

    • Helical viruses: Hollow, cylindrical capsid.

    • Polyhedral viruses: Many-sided.

    • Complex viruses: Complicated structures.

Taxonomy of Viruses

  • Viral Nomenclature: Classifies viruses into families and genera based on:

    • Viral genetics

    • Chemistry

    • Morphology

    • Mechanisms of multiplication

  • Viruses can also be informally categorized by:

    • Naked or enveloped structure

    • Type of genetic material (ssDNA, dsDNA, ssRNA, dsRNA)

    • Segmentation of genomes

    • Positive-strand (+) or negative-strand (−) RNA

Viral Life Cycle

  • For replication, a virus must:

    • Invade a host cell

    • Take over the host's metabolic machinery

Multiplication of Bacteriophages

  • Lytic Cycle:

    • Phage causes lysis and death of the host cell.

  • Lysogenic Cycle:

    • Phage DNA is integrated into host DNA.

  • Phage Conversion:

    • Results in the host cell exhibiting new properties.

  • Specialized Transduction:

    • Transfer of specific DNA fragments.

T-Even Bacteriophages: Lytic Cycle Steps
  1. Attachment: Phage attaches by tail fibers to the host cell.

  2. Penetration: Phage lysozyme opens the cell wall; tail sheath contracts to force DNA into the cell.

  3. Biosynthesis: Production of phage DNA and proteins.

  4. Maturation: Assembly of phage particles into complete virions.

  5. Release: Phage lysozyme breaks the cell wall to release new phages.

Bacteriophage Lambda (λ): Lysogenic Cycle
  • Lysogeny: Phage remains latent by integrating its DNA (prophage) into the host cell's chromosome.

  • When the host cell replicates, it also replicates prophage DNA.

  • Environmental stressors can trigger the prophage to enter the lytic cycle.

Results of Lysogeny
  • Lysogenic cells demonstrate immunity to reinfection by the same phage.

  • Example: Corynebacterium diphtheriae’s virulence is linked to a toxin produced by prophage integration.

Generalized vs. Specialized Transduction

  • Generalized Transduction:

    • Random bacterial DNA pieces transferred by a phage during the lytic cycle.

  • Specialized Transduction:

    • Occurs when the prophage is excised, carrying adjacent bacterial genes, serving those genes to a new host during infection.

Multiplication of Animal Viruses

  • The stages include:

    • Attachment: Viruses attach to the cell membrane.

    • Penetration: Entry by receptor-mediated endocytosis or membrane fusion.

    • Uncoating: By viral or host enzymes.

    • Biosynthesis: Production of viral nucleic acids and proteins.

    • Maturation: Nucleic acids assemble with capsid proteins.

    • Release: Via budding (enveloped viruses) or rupture (non-enveloped viruses).

Attachment Phase
  • Absence of receptors on host cells severely limits viral infection potential.

Penetration Methods
  • Receptor-Mediated Endocytosis:

    • Utilized by both enveloped and non-enveloped viruses.

  • Membrane Fusion: Occurs in enveloped viruses.

  • Direct Penetration: Common in non-enveloped viruses.

Comparison of Bacteriophage and Animal Virus Multiplication

Stage

Bacteriophages

Animal Viruses

Attachment

Tail fibers attach to cell wall proteins

Attaches to plasma membrane receptors

Entry

Injected viral DNA into the host cell

Entry through endocytosis or fusion

Uncoating

Not required

Enzymatic removal of capsid proteins

Biosynthesis

Occurs in host cytoplasm

In nucleus or cytoplasm depending on type of virus

Chronic Infection

Lysogeny

Latency, slow infections, cancer

Release

Host cell lysis

Budding or rupture

Types of Viral Genomes and Their Replication

  • dsDNA: Replicates in the nucleus using viral enzymes and host cell machinery.

  • ssDNA: Requires conversion to double-stranded form for replication.

  • RNA Viruses: Utilize RNA-dependent RNA polymerase for their lifecycle.

    • +ssRNA: Serves as mRNA.

    • -ssRNA: Needs conversion to +ssRNA for protein synthesis.

    • dsRNA: Examples include Rotavirus.

Replication of Retroviruses

  • Type: + Single-stranded RNA

  • Method: Uses reverse transcriptase to generate DNA from its RNA genome.

  • Viral DNA incorporates into the host DNA as a provirus.

  • Examples include HIV.

Reverse Transcriptase Activities
  1. Acts as RNA-dependent DNA polymerase to make the first DNA strand.

  2. Has RNase H activity to degrade the original viral RNA.

  3. Functions as DNA-dependent DNA polymerase to synthesize the second DNA strand from the first one.

Persistent Viral Infections

  • Definition: Virus remains in the host but is not entirely cleared.

  • Types of persistent infections:

    • Latent Virus: Remains inactive in host and can reactivate (e.g., Herpes simplex virus).

    • Chronic Virus: Continuously replicates at low levels without noticeable symptoms (e.g., HIV, Hepatitis C).

Chronic vs. Latent Infection

Feature

Chronic Viral Infection

Latent Viral Infection

Definition

Virus is continuously produced for a long time.

Virus becomes inactive within host cells.

Viral Replication

Ongoing, though may be at low levels.

Stops or is minimal during latency.

Detectability

Virus is detectable continuously.

Virus undetectable between reactivation episodes.

Immune Response

Persists despite immune responses.

Immune system cannot detect dormant virus.

Viruses and Cancer

Mechanisms of Oncogenesis
  1. Insertion of viral genes into host DNA that disrupt regulatory genes or activate proto-oncogenes, leading to uncontrolled cell division.

  2. Production of viral oncogenes associated with direct cellular transformation.

  3. Inactivation of host tumor suppressor proteins (e.g., p53, Rb).

  4. Chronic inflammation promoting DNA damage and tumor formation, along with weakened immune response.

Viruses Associated with Cancers

Virus Type

Associated Cancer(s)

Mechanism

Human papillomavirus (HPV)

Cervical, anal, oropharyngeal cancers

Inactivation of p53 and Rb proteins

Epstein-Barr virus (EBV)

Burkitt lymphoma, nasopharyngeal carcinoma

Activates growth-promoting pathways

Hepatitis B virus (HBV)

Hepatocellular carcinoma (liver cancer)

Chronic inflammation and DNA integration

Hepatitis C virus (HCV)

Hepatocellular carcinoma

Chronic inflammation without integration

Human T-cell leukemia virus type 1 (HTLV-1)

Adult T-cell leukemia

Activation of oncogenes by tax protein

Kaposi’s sarcoma-associated herpesvirus

Kaposi’s sarcoma

Encodes oncogenes and cytokine-like proteins

Merkel cell polyomavirus

Merkel cell carcinoma

Integration and expression of viral oncoproteins

Plant Viruses and Viroids

  • Plant viruses generally enter through wounds or via insect vectors due to the protective impermeable cell walls.

  • Movement strategies include:

    • Local cell-to-cell movement.

    • Systemic movement through plant vasculature (xylem & phloem).

Viroids and Virusoids
  • Viroids: Short pieces of naked RNA; known to cause diseases such as potato spindle tuber disease.

  • Virusoids: Subviral particles that require a helper virus to replicate.

Prions

  • Prions: Proteinaceous infectious particles capable of causing spongiform encephalopathies.

  • Modes of transmission:

    • Inherited and transmissible via ingestion, transplant, or surgical instruments.

  • Examples of diseases include:

    • Mad Cow Disease, Creutzfeldt-Jakob Disease (CJD), Fatal Familial Insomnia, and Sheep Scrapie.

Protein Forms
  • PrPC: Normal cellular prion protein found on cell surfaces.

  • PrPSc: Scrapies protein that accumulates in brain cells causing disease.