Viruses, Viroids, Prions, and Principles of Infectious Disease & Epidemiology

Viruses, Viroids, and Prions

Definition and Structure of Viruses and Virions

Viruses are minuscule, acellular infectious agents containing either DNA or RNA (never both). They lack a cytoplasmic membrane, cytosol, organelles, and metabolic activity, making them obligate intracellular parasites. A virion is the extracellular form of a virus, consisting of the viral genome enclosed in a protein coat, and sometimes surrounded by an envelope.

• Nucleic acid: The viral genome (DNA or RNA)

• Capsid: Protein coat surrounding the genome

• Capsomeres: Protein subunits of the capsid

• Nucleocapsid: Capsid plus nucleic acid

• Envelope (some viruses): Phospholipid membrane derived from host

• Recognition sites/glycoprotein spikes: Attachment to host cells

The capsid and envelope protect the genome and provide recognition sites for host cell identification.

Viral Genomes

Viral genomes are highly diverse and may be:

• Double-stranded DNA (dsDNA)

• Single-stranded DNA (ssDNA)

• Double-stranded RNA (dsRNA)

• Single-stranded RNA (ssRNA)

• Linear or circular

• Segmented or unimolecular

The type of genome determines the replication strategy, enzymes required, and site of replication.

Host Specificity

Viruses exhibit host specificity due to the interaction between viral surface proteins (keys) and host cell receptors (locks). Only matching receptors allow infection.

• Example: HIV infects helper T cells; West Nile virus infects multiple species.

Capsid Structure and Shapes

The capsid is a protein coat with the following functions:

• Protects the genome

• Determines viral shape

• Contains recognition sites for host attachment

• Packages genetic material

Three basic shapes:

• Helical: Spiral arrangement, tube-like

• Polyhedral: Spherical, usually icosahedral (20 sides)

• Complex: Multiple components, e.g., bacteriophages

Viral Envelope

Some viruses acquire an envelope from the host cell membrane during replication or release. The envelope contains a phospholipid bilayer, matrix proteins, and viral glycoprotein spikes.

• Functions: Host recognition, attachment, immune evasion

• Enveloped viruses: Fragile, sensitive to alcohol/detergents, better at immune evasion

• Naked viruses: More stable, resistant to environmental damage, more easily recognized by the immune system

Classification of Viruses

Viruses are classified by:

1. Type of nucleic acid (DNA or RNA)

2. Presence or absence of envelope

3. Shape

4. Size

Taxonomy includes orders, families, and genera (not kingdoms or classes).

Lytic vs. Lysogenic Replication Cycles

Feature	Lytic Cycle	Lysogenic Cycle
Outcome	Immediate replication, host cell dies	Viral DNA dormant, host survives until induction
Stages	Attachment, Entry, Synthesis, Assembly, Release	Attachment, Entry, Prophage insertion, Replication with host DNA, Induction, Lytic cycle resumes

Induction: Prophage leaves chromosome (e.g., after DNA damage) and enters lytic cycle.

Bacteriophage vs. Animal Virus Replication

Stage	Bacteriophage	Animal Virus
Attachment	Tail proteins bind cell wall	Spikes/capsid/envelope bind membrane proteins
Entry	Genome injected	Entire capsid enters (direct penetration, endocytosis, or membrane fusion)
Uncoating	Not required	Required (capsid removed)
Replication Site	Cytoplasm	RNA viruses: cytoplasm; DNA viruses: nucleus
Release	Lysis	Naked: lysis/exocytosis; Enveloped: budding
Chronic Infection	Lysogeny	Latency

Replication and Synthesis of DNA and RNA Viruses

• dsDNA viruses: Use host RNA polymerase; each DNA strand as template

• ssDNA viruses: Synthesize complementary DNA, then mRNA

• +ssRNA viruses: Genome acts as mRNA; immediate translation

• -ssRNA viruses: Viral RNA-dependent RNA polymerase makes +RNA

• dsRNA viruses: Positive strand as mRNA; each strand templates the other

• Retroviruses (+ssRNA): Use reverse transcriptase: $RNA \rightarrow DNA$; DNA integrates as provirus

Release of Viral Particles: Lysis vs. Budding

• Lysis: Cell ruptures, dies, many viruses released at once (common for phages and naked viruses)

• Budding: Virus acquires envelope from cell membrane, host may survive temporarily (common in enveloped animal viruses)

Latency in Animal Viruses

Latency is a dormant state where animal viruses remain in host cells without causing symptoms. If viral DNA integrates into host DNA, it forms a provirus (permanent). Examples: HIV, chickenpox, hepatitis B, herpes viruses.

Neoplasia, Tumors, and Cancer

• Neoplasia: Uncontrolled cell division

• Tumor: Mass of neoplastic cells

• Benign: Localized, usually not harmful

• Malignant: Invades tissues, can spread (cancer)

• Metastasis: Spread of malignant cells to distant sites

Viruses and Cancer

Viruses may cause cancer by carrying oncogenes, activating host proto-oncogenes, or interfering with tumor suppressor genes. About 20–25% of human cancers are virus-associated.

Viroids

Viroids are extremely small, circular ssRNA molecules that infect plants. They lack a capsid and do not encode proteins. Disease results from viroid RNA binding and destroying plant mRNA.

Prions

Prions are infectious proteins lacking nucleic acids. They replicate by converting normal cellular PrP (mostly alpha-helices) into abnormal prion PrP (mostly beta-pleated sheets), causing progressive brain disease.

Control and Destruction of Prions

• Prions resist standard sterilization

• Require prolonged high temperatures, strong chemicals (e.g., sodium hydroxide, bleach), or destruction of instruments

Diseases Caused by Prions

• Creutzfeldt-Jakob disease (CJD)

• Variant CJD (vCJD)

• Kuru

• Fatal Familial Insomnia (FFI)

All are transmissible spongiform encephalopathies (TSEs).

Infection, Infectious Diseases, and Epidemiology

Types of Symbiosis

• Mutualism: Both organisms benefit (e.g., gut bacteria)

• Commensalism: One benefits, other unaffected (e.g., skin mites)

• Amensalism: One harmed, other unaffected (e.g., fungus secreting antibiotics)

• Parasitism: One benefits, host harmed (e.g., Mycobacterium tuberculosis)

Relationship	Organism 1	Organism 2
Mutualism	Benefits	Benefits
Commensalism	Benefits	Unaffected
Amensalism	Harmed	Unaffected
Parasitism	Benefits	Harmed

Microbiome: Resident and Transient Members

• Resident microbiota: Permanent, stable, beneficial, hard to remove

• Transient microbiota: Temporary, easily removed, may be neutral or harmful

Resident	Transient
Permanent	Temporary
Stable population	Changing
Difficult to remove	Easily removed
Usually beneficial	May/may not be harmful

Opportunistic Infections

• Introduction into unusual site (e.g., E. coli in urethra → UTI)

• Immune suppression (e.g., HIV/AIDS, chemotherapy)

• Changes in microbiome (e.g., antibiotics → Candida overgrowth)

• Other factors: hormonal changes, stress, diet, exposure to pathogens

Reservoirs of Infection

• Human: Symptomatic/asymptomatic carriers (e.g., Typhoid Mary)

• Animal: Zoonoses (e.g., rabies, Lyme disease)

• Nonliving: Soil, water, food (contaminated by feces/urine)

Contamination vs. Infection

• Contamination: Microbes present, not necessarily multiplying

• Infection: Microbes invade, multiply, and establish in host

Portals of Entry

• Skin: Cuts, burns, abrasions, hair follicles

• Mucous membranes: Respiratory, digestive, urinary, reproductive tracts

• Placenta: Some pathogens cross to fetus

• Parenteral route: Not a true portal; via needles, bites, trauma

Adhesion Factors

• Adhesion disks: Protozoa

• Suckers/hooks: Helminths

• Ligands: Viruses (host specificity)

• Adhesins: Bacteria (fimbriae, flagella, glycocalyces)

Adhesion is essential for colonization and infection.

Biofilms

Biofilms are structured microbial communities attached to surfaces and enclosed in a protective matrix. They:

• Enhance attachment

• Protect from immune defenses and antimicrobials

• Cause persistent/chronic infections

Common sites: teeth, catheters, prosthetics.

Infection, Disease, Morbidity, Pathogenicity, Virulence

Term	Definition
Infection	Pathogen invades and multiplies
Disease	Infection causes tissue damage/abnormal function
Morbidity	State of illness/change from health
Pathogenicity	Ability to cause disease
Virulence	Severity of disease

Symptoms, Signs, and Syndromes

• Signs: Objective, measurable (fever, rash)

• Symptoms: Subjective, felt by patient (pain, fatigue)

• Syndrome: Group of signs/symptoms characteristic of a disease (e.g., AIDS)

• Asymptomatic: No symptoms, but signs may be present

Etiology

Etiology is the study of disease causes. Major categories:

• Hereditary

• Congenital

• Degenerative

• Nutritional

• Endocrine

• Neoplastic

• Iatrogenic (medical treatment)

• Idiopathic (unknown cause)

Koch's Postulates

1. Suspected pathogen present in every case

2. Isolate and grow in pure culture

3. Cause disease in healthy host

4. Re-isolate same pathogen

Limitations: Some pathogens can't be cultured, diseases may have multiple causes, ethical concerns, and some diseases are syndromes with multiple agents.

Virulence Factors

• Extracellular enzymes: Spread infection, invade tissues (e.g., coagulase, kinases)

• Toxins: Exotoxins (secreted, potent), endotoxins (Lipid A of Gram-negatives)

• Adhesion factors: Enable attachment

• Antiphagocytic factors: Capsules, chemicals preventing phagocytosis

Stages of Infectious Disease

1. Incubation: No symptoms, pathogen multiplying

2. Prodromal: Mild, nonspecific symptoms

3. Illness: Severe symptoms, peak pathogen activity

4. Decline: Symptoms improve, pathogen decreases

5. Convalescence: Recovery, tissue repair

Transmission of Pathogens

Type	Examples
Contact	Direct (touch), indirect (fomites), droplets (<1m)
Vehicle	Airborne (>1m), waterborne, foodborne, bodily fluids
Vector	Mechanical (flies), biological (mosquitoes, ticks)

Droplet vs. Airborne Transmission; Mechanical vs. Biological Vectors

Transmission Type	Key Feature	Examples
Droplet	Large droplets, <1 meter	Strep throat, whooping cough
Airborne	Aerosols, >1 meter	TB, measles, influenza
Mechanical vector	Passive carriage, no development in vector	Flies, cockroaches
Biological vector	Pathogen develops in vector	Mosquitoes, ticks

Classification of Infectious Diseases

• By taxonomic category (bacterial, viral, etc.)

• By body system affected

• By longevity/severity (acute, chronic, subacute, latent)

• By mode of transmission

• By population effects (endemic, sporadic, epidemic, pandemic)

Acute, Subacute, Chronic, and Latent Diseases

Disease Type	Development	Duration
Acute	Rapid	Short
Subacute	Intermediate	Intermediate
Chronic	Slow	Long
Latent	Dormant after infection	Symptoms appear later

Communicable, Contagious, and Noncommunicable Diseases

• Communicable: Transmitted host-to-host (e.g., TB, influenza)

• Contagious: Easily spread (e.g., measles, chickenpox)

• Noncommunicable: Not spread person-to-person (e.g., diabetes)

Epidemiology: Incidence and Prevalence

• Incidence: Number of new cases in a time period

• Prevalence: Total number of cases (new and existing)

Endemic, Sporadic, Epidemic, Pandemic

Term	Description
Endemic	Constant presence in one area
Sporadic	Occasional, scattered cases
Epidemic	Cases exceed expected level
Pandemic	Epidemic on multiple continents

Healthcare-Associated Infections (HAIs)

• Exogenous: Pathogen from healthcare environment

• Endogenous: Patient's own microbiota (opportunistic)

• Iatrogenic: Result of medical procedures

• Superinfection: Overgrowth of opportunists after antimicrobials

Contributing factors: weakened immunity, invasive procedures, long hospital stays, poor infection control, frequent antibiotic use.