Viruses and Prions Study Guide Flashcards

Classification and Characteristics of Viruses as Nonliving Microbes

• Definition and Classification: Viruses are classified as nonliving microbes due to several distinct biological limitations.

  • Lack of Metabolism: Viruses do not possess their own metabolic processes; they cannot generate energy or synthesize molecules independently.

  • Obligate Intracellular Parasites: They cannot reproduce on their own. They must infect a host cell and hijack the host's cellular machinery to manufacture new viral particles.

Comparative Biological Analysis: Viruses vs. Prokaryotes vs. Eukaryotes

• Viruses:

  • Cellular Status: Not cells and not considered alive.

  • Reproduction: Requirement of a host cell to reproduce.

  • Size: Smallest in size, requiring a microscope for visualization.

  • Filtration: Filterable, meaning they are small enough to pass through a filter.

  • Nucleus: No nucleus present.

  • Structure: Composed of a protein capsid coating (a protein shell protecting the virus) and nucleic acid.

  • Gnome (Genome) Composition: Can be either $DNA$ or $RNA$.

• Prokaryotes (Bacteria and Archaea):

  • Cellular Status: Simple cells that are considered alive.

  • Size: Bigger than viruses but smaller than eukaryotes.

  • Filtration: Not filtrable.

  • Structure: No nuclei or other membrane-bound organelles.

  • Reproduction: Replicate via Binary fission (asexual).

  • Metabolism: Exhibit metabolism to stay alive; examples include breaking down food for energy, making proteins, and growing or repairing cells.

  • Gnome (Genome) Composition: Composed of $DNA$.

• Eukaryotes (Animals, Plants, Fungi, Protists):

  • Cellular Status: Complex cells and considered alive.

  • Size: Bigger than both viruses and prokaryotes.

  • Filtration: Not filtrable.

  • Structure: Contain nuclei and membrane-bound organelles.

  • Reproduction: Replicate through Mitosis (asexual) and Meiosis (sexual).

  • Metabolism: Exhibit metabolism to stay alive; examples include breaking down food for energy, making proteins, and growing or repairing cells.

  • Gnome (Genome) Composition: Composed of $DNA$.

Viral Structures and Functions

• Capsid:

  • Function: Protects the genetic material and determines the shape of the virus.

  • Description: The protein coat surrounding the virus.

  • Protection: Guards the viral $DNA$ or $RNA$ (gnome).

  • Composition: Built from repeating protein units known as capsomeres.

• Envelope:

  • Function: Assists the virus in entering host cells and assists in evading the host immune system.

  • Description: An outer lipid (fat) membrane found in some, but not all, viruses.

  • Position: Surrounds the protein capsid.

• Spikes (Peplomers):

  • Function: Facilitate attachment to specific host cell receptors to initiate infection.

  • Description: Protein projections extending from the capsid or the envelope.

  • Composition: Often composed of glycoproteins.

• Memory Trick for Structures:

  • Capsid = Coat (protects).

  • Envelope = Extra outer layer (helps enter cells).

  • Spikes = Stick and attach (help infect cells).

Genomic Variations in Viruses

• Genetic Material Diversity: Viruses exhibit significant variation in their genomes.

• Strandedness: Viruses can be Single-stranded ($SS$) or Double-stranded ($DS$), but never both simultaneously.

  • $SS$: One single strand of genetic material.

  • $DS$: Two strands paired together.

• Configuration:

  • Linear: A straight strand.

  • Circular: Forming a closed loop.

• Segmentation:

  • Segmented: The genome is divided into several distinct pieces.

  • Non-segmented: The genome consists of one continuous piece.

Mechanisms of mRNA Production in DNA and RNA Viruses

• General Dogma: The goal is to reach the state of $mRNA$ to produce proteins ($DNA \rightarrow mRNA \rightarrow \text{Protein}$).

• DNA Viruses:

  • Double-stranded DNA (dsDNA) Viruses: These carry $dsDNA$ similar to host cells. They utilize the host's $RNA$ polymerase to synthesize $mRNA$, which is then translated.

  • Pathway: $dsDNA \rightarrow mRNA \rightarrow \text{Protein}$.

  • Single-stranded DNA (ssDNA) Viruses: These carry one strand. The host must first build a complementary strand to create $dsDNA$.

  • Pathway: $ssDNA \rightarrow dsDNA \rightarrow mRNA \rightarrow \text{Protein}$.

• RNA Viruses:

  • Positive-sense ssRNA (ssRNA+) Viruses: The viral $RNA$ acts directly as $mRNA$ (translatable gnome). The host cell translates it immediately.

  • Pathway: $ssRNA \rightarrow \text{Protein}$ (the easiest type).

  • Negative-sense ssRNA (ssRNA-) Viruses: The $RNA$ is the complement (opposite) of $mRNA$. A complementary $mRNA$ strand must be synthesized first.

  • Pathway: $ssRNA \rightarrow mRNA \rightarrow \text{Protein}$.

  • Retroviruses: These contain $RNA$ but convert it into $DNA$ using the enzyme reverse transcriptase. This $DNA$ is then used to create $mRNA$.

  • Example: $HIV$.

  • Pathway: $RNA \rightarrow DNA \rightarrow mRNA \rightarrow \text{Protein}$.

  • Double-stranded RNA (dsRNA) Viruses: These contain $dsRNA$. The strands must be separated, and one strand is used as a template for $mRNA$.

  • Pathway: $dsRNA \rightarrow mRNA \rightarrow \text{Protein}$.

Viral Genome Evolution and Mutation Rates

• Drivers of Rapid Evolution:

  1. Rapid Reproduction: Viruses replicate in very short timeframes.

  2. High Offspring Volume: Large numbers of progeny increase the mathematical probability of mutations.

  3. Lack of Proofreading in RNA Viruses: While $DNA$ viruses utilize proofreading enzymes to correct errors, $RNA$ viruses generally lack this ability, leading to faster mutation accumulation.

• Consequences of Mutation:

  • Immune system evasion.

  • Capability to infect new host species.

  • Changes in cell/tissue tropism (infecting new cell types).

  • Increased infectivity.

• Attenuated Strains: Some mutations result in weaker versions of the virus. These attenuated strains are frequently utilized in vaccine development.

• Reassortment: This occurs when two different viral strains infect a single cell simultaneously. They exchange genetic material, resulting in a completely new strain.

• Memory Trick for Evolution: $RNA$ = Rapid mutations; $DNA$ = Detects and fixes more errors.

Antigenic Drift vs. Antigenic Shift in Influenza

• Antigenic Drift:

  • Nature of Change: Small, gradual genetic changes.

  • Cause: Accumulation of mutations over time.

  • Frequency: Occurs frequently.

  • Impact: Leads to slightly different flu strains. Small mutations in the $HA$ and $NA$ spikes mean the immune system may not recognize the virus effectively, requiring updated flu vaccines every year.

  • Mnemonic: Drift = small changes over time.

• Antigenic Shift:

  • Nature of Change: Large, sudden genetic changes.

  • Cause: Reassortment (the mixing of genetic segments from different viruses in one cell).

  • Frequency: Occurs rarely.

  • Impact: Creates entirely new flu strains. Because the population has little to no immunity, this can result in worldwide outbreaks (Pandemics).

  • Mnemonic: Shift = Big change all at once.

Taxonomy and Classification of Viruses (ICTV)

• Classification Criteria: The International Committee of Taxonomy of Viruses ($ICTV$) uses the following system (Mnemonic: $D-C-E-G$):

  1. Type of Nucleic Acid (D): Whether it is a $DNA$ or $RNA$ virus.

  2. Capsid Symmetry/Shape (C):

     • Helical: Spiral-shaped.

     • Icosahedral: $20$-sided shape.

     • Complex: More complicated structures, such as those seen in bacteriophages.

  3. Presence of an Envelope (E): Enveloped (lipid membrane) or Non-enveloped (naked).

  4. Genome Architecture (G): Examples include $ssDNA$, $ssRNA$, $dsDNA$, or $dsRNA$.

• Additional Considerations:

  • Host Range: The specific organisms a virus can infect.

  • Cell/Tissue Tropism: The specific cells or tissues targeted.

  • Size.

  • Disease Characteristics.

Medically Important Viral Families and Human Pathogens

• Parvoviridae: Human parvovirus $B19$ (fifth disease).

• Papillomaviridae: Human papillomavirus ($HPV$; causes warts).

• Adenoviridae: Adenoviruses (common colds and respiratory infections).

• Hepadnaviridae: Hepatitis $B$ virus.

• Herpesviridae: Herpes simplex virus ($HSV$), Varicella-zoster virus (chickenpox/shingles).

• Poxviridae: Smallpox virus.

• Reoviridae: Ratovirus (causes diarrhea).

• Calicivirisae: Norovirus (gastroenteritis).

• Picornaviridae: Poliovirus, Hepatitis $A$ virus, Rhinoviruses (common cold).

• Flaviviridae: Hepatitis $C$ virus, West Nile Virus, Dengue fever virus.

• Togaviridae: Rubella virus.

• Retroviridae: $HIV$ ($AIDS$), human T-lymphotropic virus ($HTLV$).

• Coronaviridae: $SARS$ virus, common cold, corona virus.

• Paramyxoviridae: Measles virus, Mumps virus.

• Filoviridae: Ebola virus.

• Rhabdoviridae: Rabies virus.

• Bunyaviridae: Hantavirus.

• Orthmyxoviridae: Influenza viruses.

• Arenaviridae: Lassa fever virus.

Host Range and Tropism

• Host Range: The collection of species a virus can infect. Some are species-specific (e.g., Measles virus only infects humans), while others infect multiple species.

• Tropism: The specific tissue or cell type a virus infects. This is determined by viral surface factors (proteins) and matching receptors on host cells.

  • Broad Tropism: Infection of a wide range of host cells/tissues.

  • Narrow Tropism: Infection of only one specific cell or tissue type.

Viral Nomenclature Conventions

• Names are italicized with the first letter capitalized. Specific endings denote taxonomic levels:

  • Order: Ends in –virales (e.g., Herpesvirales).

  • Family: Ends in –viridae (e.g., Herpesviridae).

  • Subfamily: Ends in –virinae (e.g., Alphaherpesvirinae).

  • Genus: Ends in –virus (e.g., Simplexvirus).

  • Species: Italicized; the first name and proper nouns are capitalized; not abbreviated (e.g., Human herpesvirus-1, also known as Herpes simplex virus 1).

  • Common Name: Usually same as species but NOT italicized. Only proper nouns capitalized. Can be abbreviated after first use (e.g., human herpes virus-1 ($HHV-1$), or herpes simples virus-1 ($HSV-1$)).

Bacteriophage Replication cycles

• General Steps for Lytic Replication:

  1. Attachment: Phage attaches to the bacterial cell.

  2. Penetration: Phage injects its $DNA$ into the host cell.

  3. Replication: Production of viral $DNA$ and proteins.

  4. Assembly: New phage particles (virions) are assembled.

  5. Release: Host bacterial cell lyses (bursts), releasing virions into the environment.

• Lysogenic Cycle:

  • Carried out by temperate phages.

  • The lytic cycle is interrupted.

  • The phage $DNA$ integrates into the host bacterial chromosome, becoming a prophage.

  • The prophage is replicated every time the bacterium undergoes cell division; many cells eventually carry the phage gnome.

  • The prophage can remain dormant for many generations.

  • Under specific conditions, the prophage leaves the chromosome to re-enter the lytic cycle.

Phage Conversion

• Definition: Occurs when a bacteriophage carries genes for pathogenicity factors (like toxins) and integrates them into the bacterial host.

• Medical Importance: This process can turn otherwise harmless bacteria into dangerous pathogens by transferring virulence factors that increase infection severity.

Animal Virus Replication Steps

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

2. Penetration: Virus enters via Fusion or Endocytosis.

3. Uncoating: Release of the viral gnome from the protein capsid.

4. Replication: Copying of viral nucleic acid and production of viral proteins.

5. Assembly: New genomes and proteins are packaged into virions.

6. Release: Exit via Budding (enveloped viruses) or Lysis (cell bursting).

Comparison of Enveloped and Naked Animal Viruses

• Entry Differences: Naked viruses cannot use membrane fusion; they must trigger endocytosis. Enveloped viruses can use membrane fusion.

• Exit Differences: Only enveloped viruses can be released by budding (taking part of the host lipid membrane with them). Naked viruses exit via lysis, which ruptures the host cell.

Persistent vs. Acute Viral Infections

• Acute Infections: Viruses invade, replicate rapidly, and are subsequently cleared by the host immune system.

• Persistent Infections: Viruses remain in the body for extended periods. There are two types:

  • Latent Infections: The virus becomes dormant (inactive). Replication is minimal or absent during dormancy, but the virus can reactivate later, causing periodic flare-ups in cycles of inactivity and reactivation.

  • Chronic Infections: The virus is continuously present and replicates at low levels over a long period. The immune system fails to eliminate it, and low numbers of virions remain circulating in the blood.

Oncogenic Viruses (Oncoviruses)

• Definition: Viruses that cause cancer by disrupting the normal regulation of the host cell cycle, leading to uncontrolled cell division.

• Examples of Viruses and Associated Cancers:

  • Human Papillomavirus ($HPV$): Cervical, anal, and oropharyngeal cancers.

  • Epstein-Barr Virus: $B$ cell and $T$ cell lymphomas, Hodgkin’s disease.

  • Hepatitis B ($HBV$) and C ($HCV$): Liver cancer (hepatocellular carcinoma).

Laboratory Methods for Virus Cultivation

• Bacteriophages: Grown inside bacterial cells using liquid media or agar plates.

• Animal Viruses: Require living hosts, including:

  • Live animals.

  • Embryonated chicken eggs.

  • Cell/tissue culture lines (e.g., HeLa cells).

The Plaque Assay

• Definition: A lab method to measure the number of infectious viruses in a sample.

• Procedure: Cells are exposed to the virus and grown on a plate. Infected cells are destroyed (lysed).

• Plaques: Clear spots on the plate where cells have been killed.

• Utility: Used to count plaque-forming units ($PFUs$) to estimate the viral titer (concentration of infectious virions).

Detection Methods for Viruses

1. Agglutination Assays:

   • Detects viruses via antigen-antibody binding.

   • Positive result: Clumping (agglutination) of particles.

   • Advantage: Simple and quick.

   • Limitation: Requires a sufficient concentration of antigen or antibody.

2. ELISA (Enzyme-Linked Immunosorbent Assay):

   • Uses antigen-antibody binding to produce a color change.

   • Advantage: Highly sensitive; commonly used.

   • Limitation: Depends on the patient's immune response; might miss newly mutated viruses.

3. Nucleic Acid Detection (PCR, Probes, Sequencing):

   • Directly detects viral $DNA$ or $RNA$.

   • Advantage: Extremely accurate and sensitive; fast; does not depend on immune response.

   • Limitation: Requires expensive specialized equipment and known genetic targets.

Antiviral Drug Approaches

• Mechanism: Blocking different stages of the viral replication cycle.

  1. Prevention of Attachment: Antibody-based drugs like $HRIG$ stop infection before it starts.

  2. Prevention of Uncoating: Vapendavir (used for cold sores) prevents the viral gnome from leaving the capsid.

  3. Inhibition of Replication: Ribavirin (a nucleoside analog) is incorporated into the viral gnome, causing mutations and early termination of replication.

Prions and Prion Diseases

• Definition: Infectious, misfolded proteins that contain no genetic material ($DNA$ or $RNA$).

• Mechanism: They do not replicate; instead, they cause normal proteins in the brain to misfold, leading to deposits and brain damage.

• Diseases: Transmissible spongiform encephalopathies ($TSEs$), named for the sponge-like appearance of brain tissue.

  • Examples: Creutzfeldt-Jacob Disease ($CJD$), Variant Creutzfeldt-Jacob Disease, Kuru, and Fatal Familial Insomnia.

Transmission of Creutzfeldt-Jakob Disease (CJD)

1. Variant CJD (vCJD): Acquired by consuming beef contaminated with prions from "mad cow disease."

2. Sporadic CJD: Occurs spontaneously due to mutation or misfolding; affects $200-400$ people in the $US$ annually.

3. Inherited (Familial) CJD: Caused by an inherited mutation in the prion protein gene.

4. Iatrogenic CJD: Transmitted via medical procedures using contaminated instruments, tissue transplants, or medical products.

Prion-like Neurological Disorders

• Diseases such as Alzheimer’s, Parkinson’s, and Amyotrophic Lateral Sclerosis ($ALS$) are described as prion-like because they involve misfolded proteins that spread by causing normal proteins to change shape. These deposits accumulate, damaging nerve cells and leading to progressive disease.