L10-Virus(Q1-6)

What is a virus?

a non-living, acellular, biological entity / metabolically inert particle. (Obligate intracellular parasite)

Which structures are part of every virus?

genome - DNA or RNA; double- or single-stranded

capsid - protein coat

-capsomers - individual subunits that comprise the capsid

-capsomers self-assemble into a capsid

Which structures are found in some but not all viruses?

envelope - lipid bilayer derived from host cell membrane during viral budding

• note: virtually all bacteriophage are naked; animal viruses can be enveloped or naked

spikes - viral proteins or glycoproteins in the envelope
(enzymes - for replication or pathogenesis)

How are viruses different from bacteria? Contrast their size, structure, and how they reproduce. (Dr Chen)

A virus is a lot smaller than bacteria. A bacteria can be seen with a standard brightfield microscope, while a virus requires an electron microscope to be seen.

Viruses have a protein coat in the form of capsid. Capsomers are the individual subunits that comprise the capsid, capsomers self-assemble into a capsid. Meanwhile bacteria have a capsule which is made mostly of polysaccharides (large sugar molecules).

Bacteria can replicate independently via binary fission. Viruses require a host cell for their replication, obligate intracellular replication.

How does a virulent phage replicate?

exclusively through the lytic cycle.

What are the steps of lytic replication?

1.) attachment (adsorption)
2.) penetration (injection)
3.) Synthesis of Viral Genomes
4.) Assembly
5.) Release

Describe what occurs during the attachment (adsorption) step of the phage lytic replication cycle

-ligands on viruses bind to receptors on host cells

-ligands may be on spikes or capsid proteins

-highly specific; a virus can’t just infect any cell.

Describe what occurs during the penetration (injection) step of the phage lytic replication cycle

-release of the nucleic acid from the capsid

-phage: usually inject genome into bacterial cell, leaving capsid outside

Describe what occurs during synthesis of Viral Genomes step step of the phage lytic replication cycle

• -many variations of synthesis, depending on the viral genome structure (DNA or RNA; single or double stranded; + or - strand ssRNA)

• -dsDNA and ssDNA viruses: can use host enzymes to make new viral genomes

• -dsRNA and ssRNA viruses: need RNA replicase enzyme (RNA- dependent RNA Polymerase) to make new viral genomes

• -RNA replicase enzyme must be carried in the virion in a - strand RNA virus

• -retrovirus: + strand ssRNA genome but uses a dsDNA intermediate

  • -carries the enzymes reverse transcriptase and integrase

  • -DNA intermediate integrates into host genome
    
    

-early proteins: hijack the cell; force the synthesis of new viral genomes and viral coats (example of an early protein: a viral sigma factor)

Describe what occurs during Assembly step of the phage lytic replication cycle

-capsids self-assemble; genomes packaged inside

-phage assemble in the cytoplasm

Describe what occurs during release step of the phage lytic replication cycle

naked viruses: released upon host cell lysis

(note: virtually all bacteriophage are naked)

Compare and contrast the steps in the phage lytic replication cycle to the steps in an animal virus’s replication cycle. (Dr Chen)

1. Attachment (adsorption) stage: same

2. Penetration (injection) stage: different

   1. Animal viruses enter cells by fusion or endocytosis or both (endocytosis, then fusion with the endosomal membrane)

      1. Fusion: the process by which enveloped viruses merge their lipid envelope with a host cell membrane to deliver their genetic material into the cell

      2. Endocytosis: The uptake by a eukaryotic cell of substances from the environment by membrane invagination and subsequent vacuole formation. 

3. Synthesis of viral genomes: same 

4. Assembly: different

   1. -animal viruses may assemble in the nucleus or cytoplasm, depending on the virus

5. Release

(note* animal viruses can be enveloped or naked)

naked viruses: released upon host cell lysis 

-some enveloped viruses are released by budding from the plasma membrane, which doesn’t necessarily kill host cell.

•Some types of viruses instead gain their envelope by budding into the ER, ERGIC, or Golgi during the Assembly step and are released by exocytosis (such as Coronaviruses)

dsDNA and ssDNA viruses:

can use host enzymes to make new viral genomes

dsRNA and ssRNA viruses:

need RNA replicase enzyme (RNA-dependent RNA Polymerase) to make new viral genomes
(RNA replicase catalyzes the synthesis of a complementary RNA strand using an RNA template

-RNA replicase enzyme must be carried in the virion in a - strand RNA virus

retrovirus:

+ strand ssRNA genome but uses a dsDNA intermediate

-carries the enzymes reverse transcriptase and integrase
(Reverse transcriptase: Converts single-stranded viral RNA into double-stranded complementary DNA (cDNA))
(Integrase: Catalyzes the insertion of the newly formed double-stranded viral cDNA into the host cell's genome.

-DNA intermediate integrates into host genome

What does it mean if a virus is positive (+) strand RNA?

means that the virion’s RNA can serve directly as mRNA

What does it mean if a virus is negative (-) strand RNA?

means that the virion’s RNA must be first copied into a complementary strand, which then serves as mRNA

For the a - strand virus to be replicated, why MUST the - strand RNA virus carry RNA replicase enzyme (ready made) in its virion?

host cells lack the enzymes needed to synthesize mRNA or replicate RNA from an RNA template.

How are “early viral proteins” different from “late viral proteins”?

early proteins: hijack the cell; force the synthesis of new viral genomes and viral coats
late proteins: viral proteins that are part of the mature virion

What are examples of early viral proteins?

viral sigma factor, RNA Replicase, reverse transcriptase

What are examples of late viral proteins

Capsid / capsomers proteins, Tailed phage baseplates and distal tail fibers in T4 phages.

What is the eclipse period?

no mature virions present

Why does early proteins have differently- shaped curve from the others?

Early proteins are needed first to take over the host cell and start viral DNA replication. Their curve rises quickly because they are produced soon after infection.

Once replication is underway, the virus shifts toward making late proteins, such as capsid components. Early protein production slows or stops, and existing early proteins gradually break down—so their curve levels off and slightly declines.

Meanwhile, viral DNA, late proteins, and assembled viruses continue accumulating, so their curves rise later.

Define: temperate phage

A phage that has a dual reproductive strategy. Upon infecting a host cell, it can choose between entering the lytic cycle (destroying the cell) or the lysogenic cycle. In the lysogenic cycle, the viral genome integrates into the host bacterial chromosome, becoming a dormant prophage that replicates silently alongside the host cell without harming it until environmental stress triggers its activation. (Classic example: Phage lambda λ (Lambda))

Define: virulent phage

A phage that reproduces exclusively through the lytic cycle. It hijacks the host cell, rapidly manufactures new viral progeny, and aggressively destroys (lyses) the host bacterium to release them. These phages are strictly destructive and have no capacity for a dormant or integrated phase. (Classic example: Phage T4)

How is lysogenic replication different from lytic replication?
(Compare how the viral genome is replicated)

Lytic: Once injected, the viral genome is treated as a high-priority template. Viral DNA polymerases and replication complexes synthesize hundreds of standalone, linear or concatemeric copies of the viral chromosome independently of the host cell cycle.

Lysogenic: The viral genome undergoes site-specific recombination (facilitated by phage-encoded integrase enzymes) to physically insert itself directly into the host bacterial chromosome, becoming a prophage. From that point on, viral genome replication is completely outsourced to the host's own DNA replication machinery; every time the bacterium divides by binary fission, it duplicates the integrated prophage and passes an exact copy to its daughter cells.

How is lysogenic replication different from lytic replication?
(Compare What Happens to Viral Gene Expression)

Lytic: Gene expression is turned all the way up and follows a rigid, temporal cascade. Early genes hijack host resources and copy the genome; late genes flood the cytoplasm with structural capsids, tail fibers, and lysis enzymes.

Lysogenic: Viral gene expression is nearly shut down entirely, save for one critical exception: the continuous expression of a repressor protein (such as the cI repressor in phage Lambda). This repressor binds tightly to viral operators, blocking RNA polymerase from transcribing lytic genes. This maintains the dormant prophage state and grants the host cell immunity against superinfection by other identical phages.

How is lysogenic replication different from lytic replication?
(Compare What Happens to the Bacterial Host)

Lytic: The host cell is completely taken over and eventually ruptured. Its chromosomal DNA is often degraded to salvage nucleotides, and its structural integrity is destroyed by holins and endolysins.

Lysogenic: The host cell survives the infection and continues its normal metabolic life cycle. In many cases, the integrated prophage carries auxiliary genes that benefit the host—a phenomenon known as lysogenic conversion. For example, temperate phages often carry genes encoding potent bacterial exotoxins (such as the diphtheria toxin in Corynebacterium diphtheriae or Shiga toxins in certain E. coli strains), transforming a harmless bacterium into a dangerous pathogen. If the host cell later encounters severe environmental stress (such as UV radiation or DNA-damaging chemicals), the bacterial SOS response is triggered, destroying the viral repressor protein and causing the prophage to excise itself and switch into the lytic cycle (induction).

How is lysogenic replication different from lytic replication?

(general overview)

Feature	Lytic Replication Cycle	Lysogenic Replication Cycle
Primary Objective	Immediate, massive production of viral progeny and host destruction.	Long-term coexistence, passive propagation, and survival during unfavorable conditions.
Viral Genome Replication	Active & Independent: Viral DNA is rapidly copied thousands of times using viral replication enzymes and hijacked host machinery.	Passive: The viral genome is integrated into the host chromosome and copied only when the host cell replicates its own DNA during binary fission.
Viral Gene Expression	High & Sequential: Active transcription of early, middle, and late genes to build structural proteins and lysis enzymes.	Strictly Repressed: A viral repressor protein (e.g., the cI repressor) blocks all lytic genes, keeping the phage dormant.
Fate of the Bacterial Host	Cell Death: The host cell is structurally compromised by holins/endolysins and undergoes osmotic lysis.	Host Survival: The bacterium (now called a lysogen) lives, divides normally, and may gain new traits via lysogenic conversion.
Trigger / Transition	Proceeds straight through attachment, penetration, biosynthesis, maturation, and release.	Can switch to the lytic cycle via induction (triggered by DNA damage or cellular stress).

Which protein is required to maintain lysogeny for lambda phage?

the λ (lambda) repressor protein is essential for maintaining lysogeny

- the prophage is maintained with most of its genes (e.g. genes for replication, excision) silenced by the λ repressor

- the λ (lambda) repressor is a phage-encoded protein that represses the transcription of most phage genes except itself

How does phage lambda choose between lytic and lysogenic replication?

-details not entirely worked out yet.

-the decision is influenced by environmental conditions. For example, the glucose concentration in the media makes a difference.

-the Hfl protease can degrade the lambda repressor

-high [glucose] --> low [cAMP] --> high [Hfl]

-therefore, high glucose concentrations lead to increased degradation of the lambda repressor by Hfl, which favors the lytic cycle.

-other regulators are also involved.

Define Prophage Induction (also called viral induction):
Also provide an example

The pro­cess in which a change in the state of a lysogen, such as DNA damage caused by UV irradiation, prompts the prophage to excise from the host chromosome and enter the lytic cycle

-For example, exposure of a lysogen to UV light causes DNA damage which initiates the SOS response, which activates the protease activity of RecA that degrades the λ repressor.

What occurs during prophage induction?

The stable association between a lysogenic phage and its host bacterium can be interrupted, generally by conditions that threaten the life of the host cell. For example, if a lysogenic bacterium is irradiated with ultravio­let (UV) light, its prophage ­ will excise itself and replicate freely. This phenomenon, called viral induction, is a “bailing out” mechanism that allows temperate viruses to survive even if their host is killed.

True or false: A lysogenic phage has no effect on its host cell.

Explain, describing the concept of “lysogenic conversion.”

False

Consequences of lysogeny: specialized transduction and lysogenic conversion.

• Define: -Lysogenic conversion - the prophage alters the genome of the bacterium, conferring new properties (e.g pathogenicity).

A lysogenic phage does not leave its host cell unaffected. While the host cell is spared from immediate destruction and lysis, housing an integrated prophage profoundly alters its genetics, physiology, and phenotype.

• Superinfection Immunity: Once integrated, the viral repressor protein (such as the lambda CI repressor) continuously protects the host cell by blocking the entry or expression of any subsequent infections by identical phages, granting the cell immunity.

• Lysogenic Conversion: The integrated prophage often carries "passenger" or accessory genes that are expressed within the living host cell, equipping it with entirely new phenotypic traits—ranging from toxin production to altered surface receptors.

What are the 4 different outcomes of infection of an animal cell by an animal virus?

Transformation: transforms the host cell into a tumor cell → tumor cell division

Lytic/Lysis infection: death of cell and release of virus

Persistent infection: slow release of virus without cell death

Latent infection: virus present but not causing harm to cell; later emerges in lytic infection

Describe transformation infection of an animal cell by an animal virus and provide examples

In this infection, the virus permanently alters the normal cell-cycle controls and growth properties of the host cell without necessarily killing it immediately.

• Mechanism: Certain oncogenic DNA viruses (and some retroviruses) express viral regulatory proteins (such as HPV E6/E7 proteins or Adenovirus E1A) that bind to and neutralize host tumor suppressor proteins, most notably p53 and Retinoblastoma (Rb).

  • Cell Transformation: The alteration of properties and pro­cesses of eukaryotic cells caused by viral infection, including oncogenesis

• Cellular Outcome: By disabling these critical cell-cycle checkpoints, the virus forces a resting or regulated cell into continuous, unregulated division. The infected cell undergoes cellular transformation, losing contact inhibition and becoming immortalized. Over time, this uncontrolled proliferation can drive the development of malignant tumors or cancers.

Examples: Human Papillomavirus (HPV) driving cervical and oropharyngeal cancers, and Epstein-Barr Virus (EBV) driving lymphomas.

Describe Lytic/lysis infection of an animal cell by an animal virus

In this infection, the host cell is fully permissive, allowing the virus to run its complete replication cycle rapidly and aggressively.

• Mechanism: The virus enters the cell, takes over transcriptional and translational machinery, replicates its genome, and manufactures massive quantities of viral structural proteins. Progeny virions are assembled in large numbers.

• Cellular Outcome: The infection is cytocidal (cell-killing). The host cell invariably dies—either through direct osmotic lysis (in non-enveloped viruses) or by triggering host cell apoptosis (programmed cell death) due to the overwhelming accumulation of viral components and shutdown of host macromolecular synthesis.

Examples: Influenza virus, Poliovirus, and Rhinovirus.

Describe persistent infection of an animal cell by an animal virus

This infection involves the continuous, low-level shedding or release of viral progeny over an extended period.

• Mechanism: The virus replicates and exits the host cell gradually—typically via non-lytic mechanisms such as continuous budding through the plasma membrane. The host cell's machinery is not entirely shut down, allowing the cell to survive while constantly manufacturing and exporting new virions.

• Cellular Outcome: The host cell remains alive, though it may experience chronic metabolic stress or functional impairment. These infections often evade complete immune clearance, establishing long-term or lifelong reservoirs within the host organism.

Examples: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) replicating in hepatocytes.

Describe latent infection of an animal cell by an animal virus

In this infection, the virus enters the host cell but halts its replication cycle, remaining in a dormant, hidden state.

Mechanism: The viral genome is preserved inside the cell—either as a circular episome in the nucleus or integrated into host chromosomal DNA (a provirus). Viral gene expression is tightly restricted, and no progeny virions are produced.

Cellular Outcome: The host cell remains alive, healthy, and metabolically active, showing no outward signs of infection. However, the viral genome persists indefinitely. When the host experiences physiological stress, UV exposure, or immune suppression, the virus undergoes reactivation, switching out of latency into a productive lytic cycle.

Examples: Herpes Simplex Virus (HSV-1 and HSV-2) residing in sensory neurons, and Varicella-Zoster Virus (chickenpox/shingles).

Describe the steps in the replication of the 2009 A(H1N1) influenza virus.

1. Attachment and entry: Viral HA binds to sialic acid on the host cell’s surface. The virus enters an endosome, primarily through clathrin-mediated endocytosis.

2. Fusion and uncoating: As the endosome becomes acidic, HA changes shape and causes the viral envelope to fuse with the endosomal membrane. The M2 proton channel acidifies the virus’s interior, helping its internal matrix dissociate. The viral RNA–protein complexes, called vRNPs, are released into the cytoplasm.

3. Nuclear entry: Host proteins called importins carry the vRNPs through nuclear pores into the nucleus, where viral transcription and genome replication occur.

4. Viral mRNA and protein production: The PB1–PB2–PA polymerase complex makes viral mRNA through cap-snatching: PB2 captures a capped host RNA, PA cuts it, and PB1 uses the capped fragment as a primer to synthesize viral mRNA. The mRNA leaves the nucleus and is translated by host ribosomes.
   (( − ) ssRNA (infecting virus) → ( + ) ssRNA (replicating form and mRNA) → ( − ) ssRNA (progeny))

5. Genome replication: The polymerase copies negative-sense viral RNA into a full-length positive-sense complementary RNA (cRNA). This serves as the template for new negative-sense viral genomes. Newly produced RNA associates with nucleoprotein and polymerase to form new vRNPs.

6. Export and assembly: M1 and NEP help export the new vRNPs from the nucleus. The eight genome segments assemble into a bundle while traveling toward the cell membrane. Meanwhile, HA, NA, and M2 pass through the ER and Golgi to the plasma membrane.

7. Budding and release: New particles assemble and bud through the plasma membrane, acquiring their envelope. M2 helps pinch off the viral membrane, and NA removes the sialic acids holding the particles to the cell, allowing their release.

What is the role of the HA (hemagglutinin) protein in the spread of the 2009 A(H1N1) influenza virus?

Enables attachment and membrane fusion. Human-adapted strains generally recognize α2,6-linked sialic acids in the upper respiratory tract, supporting efficient transmission through respiratory droplets.
(binds to sialic acids on cells of respiratory tract; also an important role during virus uncoating in the endosome)

What is the role of the HA (hemagglutinin) protein in the spread of the 2009 A(H1N1) influenza virus?

Enables attachment and membrane fusion. Human-adapted strains generally recognize α2,6-linked sialic acids in the upper respiratory tract, supporting efficient transmission through respiratory droplets.

(binds to sialic acids on cells of respiratory tract; also an important role during virus uncoating in the endosome)

What is the role of the NA (neuraminidase) protein in the spread of the 2009 A(H1N1) influenza virus?

Enables release from infected cells, prevents new viruses from clumping together, and helps viruses move through respiratory mucus by removing sialic acids that would trap them.
(cleaves sialic acid residues; role in release/shedding of virion during budding)

What is the role of the PB1 (polymerase basic 1) protein in the spread of the 2009 A(H1N1) influenza virus?

Contains the polymerase’s catalytic center, which synthesizes viral mRNA and genome RNA, enabling production of new viruses.

What is the role of the PB2 (polymerase basic 2) protein in the spread of the 2009 A(H1N1) influenza virus?

Binds host RNA caps for cap-snatching. It also contributes to host specificity: its interactions with host proteins affect how efficiently the virus replicates in different species.

Why is the 2009 A(H1N1) influenza virus considered a “quadruple reassortant”?

because its eight-segmented, single-stranded RNA genome is a genetic mosaic assembled from four distinct viral lineages that had previously been circulating independently across different host species and geographic regions

This unique constellation arose through antigenic shift—a process where coinfection of a single host cell by multiple influenza strains allows viral RNA segments to mix and match during packaging.

2009 H1N1 = quadruple reassortant, with 4 distinct sources of the gene segments in the virus ()

Describe the steps in the replication of Coronaviruses

1. Attachment: The viral spike (S) protein binds a receptor on the host cell (the spike of SARS-CoV-2 binds to ACE2 (angiotensin-converting enzyme 2)). This interaction helps determine which species and tissues the virus can infect.

2. Entry and fusion: Host proteases cleave S, exposing its fusion peptide. The viral envelope fuses with a cellular membrane, releasing the viral RNA genome into the cytoplasm.

3. Production of replication proteins: The positive-sense RNA genome acts directly as mRNA. Host ribosomes translate it into the polyproteins pp1a and pp1ab, with ribosomal frameshifting allowing production of pp1ab. Viral proteases cut these polyproteins into nonstructural proteins, which assemble into the replicase–transcriptase complex.

4. RNA replication and transcription: This complex produces negative-strand RNA intermediates, which serve as templates for new positive-sense genomic RNA and subgenomic mRNAs. The subgenomic mRNAs encode structural and accessory proteins.

5. Structural protein production: S, membrane (M), and envelope (E) proteins are synthesized and inserted into the endoplasmic reticulum, then transported to the ER–Golgi intermediate compartment (ERGIC). Nucleocapsid (N) protein binds the new viral genomes.

6. Assembly: N-coated genomes bud into ERGIC membranes containing the viral structural proteins, producing enveloped virus particles.

7. Release: New viruses travel to the cell surface inside vesicles and leave by exocytosis.

What are two pathways for Coronavirus fusion?

Cell-surface pathway—TMPRSS2
Endosomal pathway—cathepsin L

Describe the Cell-surface pathway—TMPRSS2 of Coronavirus fusion

The host-cell surface protease TMPRSS2 cleaves and activates spikes, allowing the viral envelope to fuse directly with the cell’s plasma membrane. This pathway does not require endosomal acidification.

Describe the Endosomal pathway—cathepsin L for Coronavirus fusion?

The virus enters the cell through endocytosis. The acidic environment inside the endosome enables cathepsin L to cleave and activate spike, allowing the viral envelope to fuse with the endosomal membrane. This pathway requires endosomal acidification.

What is the relationship between TMPRSS2 expression and hydroxychloroquine effectiveness as an antiviral against SARS-CoV2? Explain. (Dr Chen

The ability of HCQ to inhibit infection by SARS-CoV2 is inversely correlated with TMPRSS2 expression levels

Compared to SARS-CoV1 S-mediated infection, SARS-CoV2 S- mediated infection relies more on the TMPRSS2 pathway than on the endosomal pathway

What is the relationship between TMPRSS2 expression and hydroxychloroquine effectiveness as an antiviral against SARS-CoV2? Explain. (chat)

• Higher TMPRSS2 expression makes hydroxychloroquine less effective at blocking SARS-CoV-2 entry.

• Hydroxychloroquine raises endosomal pH, interfering with the activity of cathepsin L, the enzyme that cleaves and activates spike in the endosomal pathway. Therefore, it effectively inhibits entry when the virus relies on this pathway.

• TMPRSS2 provides an alternative route: it cleaves and activates spike at the cell surface, allowing fusion without requiring endosomal acidification. Hydroxychloroquine does not block this route, so greater TMPRSS2 expression allows the virus to bypass the drug’s effect.

What was the question that Luria and Delbrück sought to answer with their experiment?

Do mutations in bacteria that confer resistance to phage occur spontaneously, or are the mutations caused by phage?

Describe how  Luria and Delbrück’s experimental results led to their conclusion:

They grew a large number of separate cultures of susceptible bacteria, each from an inoculum too small to likely contain phage-­resistant cells. When the cultures ­were fully grown, a sample from each was mixed with phage and plated. The number of resistant colonies that developed was highly variable —­ much more variable than multiple samples taken from a single culture. ­ These results convincingly fit a mathematical model (the Poisson distribution) that predicts the highly variable number of mutants that arise randomly in the individual cultures. The cultures where mutations occurred early in their growth would have large numbers of resistant progeny cells, whereas mutations occurring ­ later would have fewer resistant progeny (hence, “fluctuation”). If phage re­sis­tance ­were the result of exposure to the phages, the variation among samples from dif­fer­ent cultures and from the same culture would be similar (“no fluctuation”).

Describe how their experimental results led to their conclusion. What results would have supported the alternate hypothesis? (Dr Chen)

Their conclusion:
Phage resistance mutations occur spontaneously and are selected for by the phage, based on the fluctuation in the number of phage resistant progenies.

Alternate conclusion:
If phages were causing the mutation, then we would expect the same number of phage resistant bacteria (no fluctuation).

What is a prion and how is it believed to cause disease?

Prion - an infectious proteinaceous particle.

Prions are thought to be incorrectly folded proteins, which can then induce other proteins to be incorrectly folded, and aggregate together. (Destroying protein and cell function.) Only certain proteins (such as PrP) can become prions.

What are the characteristics of prions that makes them different from a virus?

1. resistant to inactivation by heating to 90oC, a temperature that will inactivate viruses.

2. not sensitive to radiation, which ordinarily damages virus genomes

3. not destroyed by enzymes that digest RNA or DNA

4. sensitive to protein denaturing agents

How is a prion different from a virus? (overall)

Feature	Prion	Virus
Composition	Protein only. Completely devoid of any nucleic acid (zero DNA or RNA).	Nucleic acid + Protein capsid. Contains a DNA or RNA genome enclosed within a protein coat (and often a lipid envelope).
Replication Mechanism	Conformational Templating: Acts as a structural template, forcing normal host proteins (PrPC) to refold into the pathogenic -sheet isoform (PrPSc).	Cellular Hijacking: Uses viral and host polymerases to transcribe, translate, and copy its genetic code to build new progeny.
Host Immune Response	None. Because prions are misfolded versions of normal host self-proteins, they do not trigger an inflammatory or adaptive immune response (immunological tolerance).	Robust: Readily recognized as foreign, triggering strong innate and adaptive immune responses (interferons, neutralizing antibodies, cytotoxic T-cells).
Physical & Chemical Stability	Extremely resilient: Highly resistant to standard sterilization methods, boiling, UV radiation, formalin, and nucleases due to stable amyloid aggregates.	Sensitive: Readily inactivated by standard heat, UV irradiation, detergents, and chemical disinfectants that destroy nucleic acids or lipid envelopes.
Coding Capacity	Zero genes: Carries no genetic blueprint; information is stored entirely in its tertiary/quaternary protein conformation.	Carries genetic code: Contains genes encoding structural proteins, enzymes, and regulatory factors required for infection.