Class 16 Virus, Viroids and Prions

Origin Story - Cells

• Cellular life arose once.
• Evolution was linear, with branches.
• Cellular life forms share a common heritage, allowing for a timeline to be mapped.

Origin Story - Viruses

• Viruses arose multiple times, from diverse cell types.
• They use various strategies and components.
• Viruses are frequently restricted to a limited range of host cells.
• Viruses use nucleic acids (RNA or DNA) to store information.
• Viruses use the same genetic codes as living cells and evolve through genetic mutations.
• The size of their genomes influences the amount of information they can store.
• All viruses use proteins but the specific proteins and how they are used vary widely.
• Virus classification has a naming convention, but it is less useful compared to the system for cellular life.

Informal Taxonomy

• Groups of unrelated viruses share similar routes of infection.
  • Enteric viruses use the oral-fecal route.
  • Respiratory viruses spread via inhalation.
  • Arboviruses are spread by vectors.
  • Sexually transmitted infections (STI/STD)
  • Zoonotic viruses spread from animals.

Two General Stages of Viruses

• Virion: Consists of protein and nucleic acid.
  • It is the infective stage and primarily protein based.
  • Some virions have a membrane envelope.
• Viruses do not have metabolic functions and can persist for many years.
• Infected cell: Viruses primarily hijack cell systems and their nucleic acids enter the cell. Replications require a host cell.

Structure - Protein Capsid

• Viruses have a limited number of proteins for their small size.
• Capsid structures are constructed using "lego-like" proteins.

Three Basic Shapes of Viruses

• Icosahedral (20 flat triangles)
• Helical
• Complex (bacteriophages, often ancillary proteins)

Virion Structure Example 1

• Virion is a viral particle, a nucleic acid surrounded by a protein coat (capsid).
• The capsid is made of identical subunits called capsomeres.
• The capsid and nucleic acids together make a nucleocapsid.
• Some viruses are surrounded by a lipid bilayer (envelope) from the host cell.

First Focus: Bacteriophages

• Lytic and Temperate phages, which interact with organisms in different ways.
  • Lytic phages always result in cell destruction.
  • Temperate phages can transition between lytic and lysogenic states.
  • Filamentous phages produce virus continuously without killing the cell.

Diagram of Three Types of Bacteriophage Infection

• Lytic infections eventually kill host cell.
• Lysogenic infections insert genetic material into the host genome.
• Productive Infections have continuous production of virus, without destroying the cell.

Lytic Phage Infection (Example T4)

• T4 is a complex phage with double-stranded DNA.
• Attachment is by tail fibers.
• Genome entry involves a small hole created in the cell wall by a phage lysozyme.
• Only the DNA travels into the cell.

Lytic Phage Infection (cont.)

• Synthesis stage: Early genes are transcribed and translated following entry of the genome.
• Host cell resources are used to create new viral components.
• The host DNA is destroyed by phage enzymes.
• New DNA polymerases are created for viral replication.

Lytic Phage Infection (cont.)

• Assembly stage: Viral components self-assemble into new phages.
• Hundreds of infectious virions are assembled inside the host cell.

Lytic Phage Infection (cont.)

• Release stage: Lysis (destruction) of the host cell releases viral particles.
• A phage enzyme degrades the cell wall.

Temperate Phage (Example Lambda Phage)

• Double-stranded DNA that infects E. coli
• Attachment and genome entry are similar to T4.
• After entry, the linear chromosome circularizes.
• The pathway can transition to lytic infections.

Lysogenic Infection

• The phage genome integrates into the host chromosome.
• The phage DNA becomes a prophage.
• Lysogen maintains the prophage, and multiplies with the host cell.
• Certain stressors cause viruses to enter a lytic infection cycle.

Lysogenic Infection (cont.)

• Prophage can remain latent for multiple host cell division cycles.
• Phage can be induced to exit the lysogenic cycle under stressful conditions, such as exposure to UV light.
• Lysogeny provides immunity to superinfection, which is a crucial feature for virus persistence.

Filamentous (Helical) Phage - Example M13.

• Single-stranded (+) DNA genome.
• Filamentous phages infect the F-pilus.
• DNA is enclosed within an icosahedral head.

Assembly - M13

• Capsomeres insert into cytoplasmic membrane.
• Phage proteins span the cell wall and the outer membrane.
• DNA is continually released while the cell stays alive.

SEA-PHAGES

• Freshman students' research isolating and sequencing bacteriophages.
• Phage research is growing as a model for phage therapy.

Animal Viruses

• Viruses that infect animals, including humans.
• Infection and enzymes are a critical detail for understanding transmission and developing antiviral agents.
• Cellular organization is complex in animals compared to bacteria.

Animal Viruses - Attachment (Adsorption)

• Viruses attach to specific receptors on the host cell surface, often glycoproteins on the cytoplasmic membrane.
• More than one receptor is typically needed for successful infection.
• Viral attachment is critical. The receptor specificity limits the range of cells that can be infected.

Enveloped Viruses (Option 1 - Membrane Fusion)

• Viral infection begins with the virus envelope fusing with the host cell membrane.
• The nucleocapsid is released inside.
• Viruses then use host cell machinery to replicate.

Option 2 - Enveloped or Non-enveloped.

• Enveloped viruses fuse with the host cell membrane.
• Non-enveloped viruses are engulfed by the host cell or enter using other means.

Next Steps

• Viruses replicate their genomes and produce viral proteins based on the type of nucleic acid present.

A Moment of Explanation on (+) and (-)

• Single-stranded RNAs have either (+) or (-) designation.
• (+) ssRNA is read directly by ribosomes to make protein.
• (-) ssRNA requires synthesis into (+) form.

Animal Virus Synthesis

• Expression of viral genes in order to make structural and catalytic viral genes.

dsDNA

• dsDNA is replicated to form viral genome and transcribed to produce mRNA in order to allow translation to form viral proteins.
• Complementary strand is transcribed.

ssDNA, (+) and (-)

• Replication process for ssDNA viruses, which includes the production of complementary strands.

Replication of RNA Viruses

• The replication of RNA viruses occurs in the cell cytoplasm rather than nucleus.
• RNA viruses encode replication enzymes.
• ssRNA(+) serve as mRNA, unlike ssRNA(-) which require transcription to form mRNA for translation processes.

Replication of ssRNA(-) Viruses

• Replication enzyme is needed for RNA genome replication.
• (+) strand is synthesised and used to make viral mRNA.

Replication of dsRNA Viruses.

• Replication enzyme is required to facilitate dsRNA replication.
• (+) strand copies are produced for viral mRNA synthesis.

RNA Viruses Encourage Mutations

• Replicases lack proofreading, which leads to more mutations for RNA viruses.
• Frequent mutations make previous immunity less effective.

Retroviruses... Special ssRNA(+) Viruses

• Contain RNA-dependent DNA polymerases (reverse transcriptase).
• RNA is transcribed to DNA and integrated into the host's DNA.

Assembly of Virons

• Viruses assemble their components into new virions.
• Some use their genome as a scaffold for assembly
• Others assemble a procapsid which encapsulates their components.

Release of Virions – Non-enveloped Viruses

• Mature virions assemble inside the host cell.
• Cell lysis releases virions.

Release of Virions – Enveloped Viruses

• Viral proteins penetrate the cytoplasmic membrane.
• Virus capsids become surrounded by host cellular membranes.
• New enveloped viruses extrude through the membrane.

Kinds of Viral Infections in Humans

• Acute infections: Rapid onset, short duration.
• Persistent infections: Last for a long time.

Persistent Infections

• Chronic infections: continuous low-level production of viruses.
• Latent infections: viral genomes persist in a latent state.

Latent Infections

• Virus integrates into host chromosomes or replicates separately, often in a non-productive way.
• Infections can reactivate and cause new rounds of productive infection.
• Examples are HSV and VZV

Viroids

• Small circular RNA molecules that cause disease in plants.
• Replicate by interacting with host cell mechanisms.

Prions

• Infectious proteins that cause disease in humans and animals.
• Linked to slow, fatal diseases.
• Composed entirely of proteins, without nucleic acids.

In Disease, Prion Proteins Accumulate in Neural Tissue

• Neurons die due to prion accumulation.
• Tissues develop holes due to prion aggregation.
• Brain function deteriorates..
• Characteristic appearance in diseased brains.

Mode of Action - Folding Rearrangement

• Normal cellular proteins (PrP^c) can be mutated to misfolded versions leading to prion aggregation.
• Infectious prion proteins (PrP^Sc) cause misfolding of normal proteins.
• Misfolded proteins aggregate, damaging tissues.