Module 10: Subviral Agents

Virology

Subviral Agents

_________________:

_________________ are infectious agents that are simpler than viruses. They are dependent on host cells or other viruses for their replication. Examples include:

1. Satellites

2. Viroids

3. Hepatitis Delta Virus

4. Prions

5. Gene Transfer Agents

6. Virophages

Satellites

__________ are subviral agents that depend on a helper virus for their replication. They can be of two types:

1. __________ viruses: Encode their own structural proteins for encapsulating their genome and forming distinct particles.

2. __________ RNAs: Packaged by the helper virus's protein. They rely on the helper virus for replication and may or may not encode proteins.

Key Features:

• Can have ssRNA, DNA, or sRNA genomes.

• Lack the necessary genes for independent replication.

• Cause distinct plant diseases.

Viroids

_________:

_________ are the smallest known infectious agents composed only of circular ssRNA (120-475 nucleotides). Unlike viruses:

• They have no coat (capsid/envelope) and do not code for proteins.

• Some viroids are ribozymes, meaning they have enzymatic activity required for replication.

• They infect plants and are parasites of the host transcription machinery, unlike viruses that exploit translation machinery.

Example of ________:

1. Potato Spindle Tuber ________(PSTVd):

   • First studied in 1967.

   • A prototype for the smallest nucleic acid-based infectious agents.

   • Causes destructive potato diseases, producing oblong tubers.

2. Cadang-cadang Coconut ________(CCCVd):

   • Causes lethal coconut palm disease.

3. Hop Latent ________(HLVd):

   • No symptoms in hops, so beer production remains unaffected.

4. Apple Scar Skin ________(ASSVd):

   • Causes mild symptoms in apples, affecting their appearance but not taste.

Hepatitis Delta Agent

_______________:

• Shares properties of both viroids and satellites.

• It requires Hepatitis B virus (HBV) as a helper virus for replication.

• Increases the severity of HBV-associated liver diseases.

1. Potato Spindle Tuber Viroid (PSTVd)

Example of Viroids:

1. ____________________:

   • First studied in 1967.

   • A prototype for the smallest nucleic acid-based infectious agents.

   • Causes destructive potato diseases, producing oblong tubers.

2. Cadang-cadang Coconut Viroid (CCCVd):

   • Causes lethal coconut palm disease.

3. Hop Latent Viroid (HLVd):

   • No symptoms in hops, so beer production remains unaffected.

4. Apple Scar Skin Viroid (ASSVd):

   • Causes mild symptoms in apples, affecting their appearance but not taste.

1. Cadang-cadang Coconut Viroid (CCCVd)

Example of Viroids:

1. Potato Spindle Tuber Viroid (PSTVd):

   • First studied in 1967.

   • A prototype for the smallest nucleic acid-based infectious agents.

   • Causes destructive potato diseases, producing oblong tubers.

2. _________________:

   • Causes lethal coconut palm disease.

3. Hop Latent Viroid (HLVd):

   • No symptoms in hops, so beer production remains unaffected.

4. Apple Scar Skin Viroid (ASSVd):

   • Causes mild symptoms in apples, affecting their appearance but not taste.

1. Hop Latent Viroid (HLVd)

Example of Viroids:

1. Potato Spindle Tuber Viroid (PSTVd):

   • First studied in 1967.

   • A prototype for the smallest nucleic acid-based infectious agents.

   • Causes destructive potato diseases, producing oblong tubers.

2. Cadang-cadang Coconut Viroid (CCCVd):

   • Causes lethal coconut palm disease.

3. _____________:

   • No symptoms in hops, so beer production remains unaffected.

4. Apple Scar Skin Viroid (ASSVd):

   • Causes mild symptoms in apples, affecting their appearance but not taste.

1. Apple Scar Skin Viroid (ASSVd)

Example of Viroids:

1. Potato Spindle Tuber Viroid (PSTVd):

   • First studied in 1967.

   • A prototype for the smallest nucleic acid-based infectious agents.

   • Causes destructive potato diseases, producing oblong tubers.

2. Cadang-cadang Coconut Viroid (CCCVd):

   • Causes lethal coconut palm disease.

3. Hop Latent Viroid (HLVd):

   • No symptoms in hops, so beer production remains unaffected.

4. ____________________:

   • Causes mild symptoms in apples, affecting their appearance but not taste.

Hepatitis Delta Virus (HDV)

____________________:

__________ is a defective subviral agent that requires Hepatitis B Virus (HBV) as a helper virus for its replication and infectivity.

Key Features:

1. Structure:

   • Size: Approximately 35 nm in diameter.

   • Genome: Contains a single-stranded, circular RNA genome of negative polarity (-ssRNA), consisting of about 1,700 nucleotides.

   • Envelope: Obtains its envelope from HBV, using HBV's surface antigens (HbsAg).

2. Dependency on HBV:

   • HDV cannot replicate or assemble without the HBV envelope proteins.

   • It uses HBV's coat to complete its life cycle, enhancing the pathogenic potential of HBV infections.

3. Comparison to Viroids:

   • HDV resembles viroids in its small, circular RNA genome and ribozyme activity.

   • However, HDV differs from viroids because it encodes the delta antigen, a protein required for its replication.

4. Delta Antigen:

   • HDV codes for a protein called the delta antigen, which exists in two forms:

     • Large delta antigen (L): Essential for viral particle assembly.

     • Small delta antigen (S): Facilitates replication.

   • The delta antigen has ribozyme activity for self-cleavage and replication of the RNA genome.

5. Replication Mechanism:

   • HDV replicates using a rolling-circle mechanism, similar to viroids.

   • The RNA genome undergoes self-cleavage during replication due to its ribozyme properties.

6. Pathogenesis:

   • HDV exacerbates HBV-related liver disease, leading to more severe outcomes such as liver cirrhosis or hepatocellular carcinoma.

   • Co-infection with HBV and HDV results in more severe liver damage than HBV alone.

7. Prevention:

   • Vaccination against HBV prevents HDV infection, as HDV cannot propagate without HBV.

• delta antigen

• HDV codes for a protein called the ___________, which exists in two forms:

  • Large___________ (L): Essential for viral particle assembly.

  • Small ___________ (S): Facilitates replication.

• The delta antigen has ribozyme activity for self-cleavage and replication of the RNA genome.

• rolling-circle mechanism

1. Replication Mechanism:

   • HDV replicates using a ___________, similar to viroids.

   • The RNA genome undergoes self-cleavage during replication due to its ribozyme properties.

Prions

What Are _________?

_________ are proteinaceous infectious particles that cause diseases by inducing normal cellular proteins to misfold into an abnormal shape.

1. Normal _________ Protein (PrPc):

   • Encoded by the Prnp gene on chromosome 20 in humans.

   • Found in many cell types, especially central nervous system (CNS) cells.

   • Functions of PrPc include maintaining neuronal health and signaling.

2. Abnormal _________ Protein (PrPSc):

   • Misfolded form of PrPc, named PrPSc because it was first discovered in scrapie (a disease in sheep).

   • Has a different secondary structure:

     • Normal PrPc: Rich in alpha-helices.

     • PrPSc: Beta-sheet rich structure, making it protease-resistant.

Normal Prion Protein (PrPc)

______________:

• Encoded by the Prnp gene on chromosome 20 in humans.

• Found in many cell types, especially central nervous system (CNS) cells.

• Functions of ______ include maintaining neuronal health and signaling.

Abnormal Prion Protein (PrPSc)

____________:

• Misfolded form of PrPc, named _________ because it was first discovered in scrapie (a disease in sheep).

• Has a different secondary structure:

  • Normal PrPc: Rich in alpha-helices.

  • _________: Beta-sheet rich structure, making it protease-resistant.

• template-directed misfolding

Mechanism of Disease:

1. Conversion Process:

   • PrPSc interacts with normal PrPc proteins and induces them to misfold into the PrPSc form, a process known as _____________.

2. Aggregation:

   • Misfolded prions aggregate into insoluble clumps in neural cells.

   • These aggregates are resistant to proteases, leading to their accumulation.

3. Effects:

   • The accumulation of prions disrupts normal neuronal functions, eventually causing neurodegeneration.

   • Leads to spongiform changes (appearance of sponge-like holes) in brain tissues.

transmissible spongiform encephalopathies (TSEs)

Diseases Caused by Prions:

Prion diseases are collectively called _____________. Examples include:

1. In Humans:

   • Creutzfeldt-Jakob Disease (CJD): Rapidly progressive neurodegenerative disease.

   • Kuru: Associated with ritualistic cannibalism in specific tribes.

   • Fatal Familial Insomnia (FFI): Genetic prion disease causing severe insomnia.

   • Gerstmann-Sträussler-Scheinker Syndrome (GSS): Inherited prion disease.

2. In Animals:

   • Scrapie: Affects sheep and goats.

   • Bovine Spongiform Encephalopathy (BSE): "Mad cow disease" in cattle.

   • Chronic Wasting Disease (CWD): Affects deer and elk.

Unique Characteristics of Prions

_______________:

• No nucleic acids: Unlike viruses or bacteria, prions lack DNA or RNA.

• Protease resistance: PrPSc is resistant to degradation by proteases, making it harder to remove or destroy.

• Highly transmissible: Prion diseases can spread via contaminated tissue, surgical instruments, or genetically.

Historical Timeline of Prions

________________

1. 1700s: Discovery of Scrapie

   • Scrapie is a fatal neurodegenerative disease affecting sheep and goats.

   • It was observed to spread within herds, indicating an infectious component.

   • Scrapie marked the first recognized prion disease.

2. 1950s: Kuru Epidemic in Papua New Guinea

   • Members of the Fore tribe in Papua New Guinea were affected by a disease called Kuru, characterized by progressive loss of motor control and eventual death.

   • Kuru was linked to ritualistic cannibalism, where infected human tissues were consumed during funerary practices.

   • This discovery highlighted prion transmission through contaminated tissues.

3. 1982: Stanley Prusiner's "Rogue Protein" Hypothesis

   • Stanley Prusiner proposed that the causative agent of prion diseases was not a conventional pathogen like a virus or bacteria, but a misfolded protein.

   • He coined the term prion (derived from protein and infection) to describe these infectious proteins.

   • His idea revolutionized biology and medicine, challenging the central dogma that nucleic acids are required for infectious agents.

4. 1986: Mad Cow Disease Outbreak

   • An epidemic of Bovine Spongiform Encephalopathy (BSE), commonly called Mad Cow Disease, occurred in the UK.

   • The outbreak was linked to the use of contaminated animal feed containing prion-infected material.

   • This led to widespread study and awareness of prion diseases in humans and animals.

5. 1997: Nobel Prize in Medicine

   • Stanley Prusiner was awarded the Nobel Prize for his groundbreaking work in understanding prions as infectious agents without nucleic acids.

1. Stanley Prusiner

1. 1982: ____________'s "Rogue Protein" Hypothesis

   • ____________ proposed that the causative agent of prion diseases was not a conventional pathogen like a virus or bacteria, but a misfolded protein.

   • He coined the term prion (derived from protein and infection) to describe these infectious proteins.

   • His idea revolutionized biology and medicine, challenging the central dogma that nucleic acids are required for infectious agents.

Characteristics of Prion Diseases

________________:

• Encephalopathy: Prion diseases cause spongiform changes in the brain, leading to neuronal death and brain tissue damage.

• Transmission:

  • 1% of cases arise by infection (e.g., contaminated meat or medical instruments).

  • Most cases are sporadic or inherited (genetic mutations in the Prnp gene).

• Fatal: All prion diseases are incurable and result in death.

Scrapie

Found in sheep and goats.

Diseases in Animals Prions

Transmissible Mink Encephalopathy (TME)

Affects mink

Diseases in Animals Prions

Chronic Wasting Disease (CWD)

Occurs in mule deer, elk, and moose

Diseases in Animals Prions

Bovine Spongiform Encephalopathy (BSE)

Known as "mad cow disease," it affects cattle.

Diseases in Animals Prions

Exotic Ungulate Encephalopathy (EUE)

Found in animals like nyala and greater kudu.

Diseases in Animals Prions

Feline Spongiform Encephalopathy (FSE)

Affects both domestic and wild cats.

Diseases in Animals Prions

Creutzfeldt-Jakob Disease (CJD

A rare, degenerative brain disorder in humans.

Diseases in Humans Prions

Kuru

Historically found in Papua New Guinea, associated with ritual cannibalism.

Diseases in Humans Prions

Gerstmann-Sträussler-Scheinker Syndrome (GSS)

A genetic form of TSE in humans

Diseases in Humans Prions

Fatal Familial Insomnia (FFI)

A hereditary TSE causing sleep disturbances and ultimately death

Diseases in Humans Prions

Gene Transfer Agents (GTAs)

_________________:

• _________________ are virus-like particles that facilitate the exchange of genetic material between bacteria, but they are not true viruses.

• Characteristics:

  1. Structure: Resemble small-tailed bacteriophages (viruses that infect bacteria).

  2. Plaque formation: Lack plaque-forming activity, meaning they cannot form clear zones of infection like traditional bacteriophages.

  3. DNA: Contain linear double-stranded DNA (dsDNA) of approximately 4.5 kilobases (kb).

  4. DNA packaging: Package DNA indiscriminately, meaning any DNA from the host cell can be included.

  5. Function: Only transfer host DNA to recipient cells rather than their own genome, acting solely as a tool for horizontal gene transfer.

  6. Purpose: They are evolved as genetic exchange vectors rather than being infectious agents.

Virophages

___________:

• ___________ are a unique type of virus that parasitize giant viruses, interfering with their replication while using the same host organism.

• Characteristics:

  1. Etymology: Derived from the Greek "phagein," meaning "to eat," hence referred to as "virus eaters."

  2. Genetics: Contain circular double-stranded DNA (dsDNA).

  3. Structure: Have icosahedral symmetry (a spherical shape with 20 triangular faces).

  4. Replication: Can only replicate in host cells that are already infected by a giant virus (a helper virus).

  5. Interference: Compete with and interfere with the replication of the giant virus, reducing its efficiency.

Examples of Virophages

_________________:

The table lists various virophages, their location, host giant viruses, and associated eukaryotic organisms. Key points include:

• Sputnik: Found in cooling towers in France, parasitizes Acanthamoeba polyphaga mimivirus.

• Mavirus: Found in Texas coastal waters, infects Cafeteria roenbergensis virus, a marine flagellate.

• OLV: Found in Organic Lake, a hypersaline Antarctic lake; it parasitizes large DNA viruses infecting Prasinophytes.

• YSLV series: Found in Yellowstone Lake, targeting various giant viruses associated with microorganisms.

• ALM: Found in Ace Lake, Antarctica, parasitizing giant viruses infecting phagotrophic protozoans.