Viruses, Pathogenesis, and Host Interactions: Study Notes for Microbiology Exam 4

Viruses: Structure, Classification, and Replication

What is a Virus? Differences Between Viruses and Bacteria

• Viruses are acellular infectious agents, typically 20–1000 nm in size, composed of a single type of nucleic acid (DNA or RNA) surrounded by a protein coat (capsid), and sometimes a lipid envelope.

• Living Status: Viruses are not considered living outside a host cell; they are inert until they infect a host, where they become metabolically active and replicate.

• Reproduction: Viruses require a living host cell for replication, utilizing the host's cellular machinery.

• Metabolism: Viruses lack metabolic enzymes and cannot generate ATP independently.

• Bacteria are larger, have both DNA and RNA, possess a plasma membrane and ribosomes, and can reproduce independently via binary fission.

Key Differences Table:

Feature	Viruses	Bacteria
Cellular Structure	Acellular	Cellular (prokaryotic)
Genetic Material	DNA or RNA (never both)	Both DNA and RNA
Reproduction	Obligate intracellular	Binary fission (independent)
Metabolism	None	Own metabolic pathways
Size	20–1000 nm	~0.5–5 μm

Classification of Viruses

• Baltimore Classification System: Categorizes viruses into seven groups based on nucleic acid type and replication strategy (e.g., Group VI: retroviruses; Group VII: DNA viruses using reverse transcriptase).

• Viral Taxonomy: The International Committee on Taxonomy of Viruses (ICTV) classifies viruses into orders, families (ending in -viridae), genera (-virus), and species.

• Viral Species: Defined by shared characteristics such as morphology, genes, enzymes, and ecological niche.

Purification and Cultivation of Viruses in the Laboratory

• Cell Culture: Viruses are grown in continuous cell lines (e.g., HeLa cells) for isolation and study. Cultures must be monitored to prevent contamination.

• Bacteriophage Cultivation: Bacteriophages are grown using the plaque method, where clear zones (plaques) on bacterial lawns indicate viral presence.

• Viral Identification: Methods include serological assays (e.g., ELISA), observation of cytopathic effects, and PCR-based techniques.

Replication: Bacteriophage vs. Animal Virus

Step	Bacteriophage	Animal Virus
Attachment	Tail fibers to cell wall proteins	Capsid/spikes to plasma membrane proteins/glycoproteins
Entry	Injection of DNA	Endocytosis or fusion (capsid enters)
Uncoating	Not required	Enzymatic removal of capsid
Biosynthesis	Cytoplasm	Nucleus (DNA viruses) or cytoplasm (RNA viruses)
Chronic Infection	Lysogeny	Latency, slow infections, or cancer
Release	Host cell lysis	Budding (enveloped) or lysis (nonenveloped)

RNA Viruses vs. DNA Viruses

• Genetic Material: RNA viruses have RNA; DNA viruses have DNA.

• Replication Site: RNA viruses usually replicate in the cytoplasm; DNA viruses often in the nucleus.

• Enzymes: RNA viruses use RNA-dependent RNA polymerase (not found in host cells).

• Mutation Rate: RNA viruses mutate more rapidly due to lack of proofreading.

• Example: SARS-CoV-2 is a single-stranded RNA virus.

Antigenic Shift in Influenza Viruses

• Influenza A viruses have a segmented RNA genome (8 segments), allowing for antigenic shift—a major genetic reassortment when two strains infect the same cell.

• This can create new combinations of surface antigens (hemagglutinin and neuraminidase), leading to pandemics.

• Mixing often occurs in pigs, which can be infected by both human and avian influenza viruses.

Viruses and Cancer (Oncogenesis)

• Some viruses cause cancer by integrating into host DNA, causing chromosomal breakage, or activating oncogenes.

• Transformed cells lose contact inhibition and grow uncontrollably.

• Examples: Retroviruses (HTLV-1, HTLV-2), DNA viruses (e.g., HPV, hepatitis B).

Bacteriophage Life Cycles

• Lytic Cycle: Phage attaches, injects DNA, replicates, assembles, and lyses host cell to release new phages.

• Lysogenic Cycle: Phage DNA integrates into host genome (prophage), replicates with host, can later enter lytic cycle.

• Animal viruses may also have latent or chronic cycles, sometimes integrating into host DNA (e.g., retroviruses).

Prions

• Prions are infectious proteins (no nucleic acid) that cause neurodegenerative diseases by inducing misfolding of normal proteins (PrPC to PrPSc).

• Misfolded proteins aggregate, damaging brain tissue (e.g., Creutzfeldt-Jakob disease).

Principles of Disease and Epidemiology

Etiology vs. Pathogenesis

• Etiology: Study of the cause or origin of a disease (e.g., Mycobacterium tuberculosis causes tuberculosis).

• Pathogenesis: Study of the development and progression of disease after the cause is established.

Types of Human Microbiota

• Normal Microbiota: Permanent residents, usually non-pathogenic (e.g., Escherichia coli in intestines).

• Transient Microbiota: Temporary residents, present for days to months.

• Microbial Diversity by Region: Skin (low moisture), eyes (protected by tears), nose/throat (mucus), mouth (nutrient-rich), large intestine (most abundant), urinary/genital systems (pH-influenced).

Types of Symbiotic Relationships

• Commensalism: One benefits, other unaffected (e.g., Staphylococcus epidermidis on skin).

• Mutualism: Both benefit (e.g., E. coli in intestine).

• Parasitism: One benefits at other's expense (e.g., influenza virus in humans).

Sepsis

• Sepsis: Systemic inflammatory response to infection, may progress to severe sepsis (organ dysfunction) and septic shock (low blood pressure).

• Signs: Fever, chills, rapid breathing/heart rate. High mortality if untreated.

Signs vs. Symptoms

• Signs: Objective, measurable (e.g., fever, rash).

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

• Example (Sepsis): Signs—fever, lymphangitis; Symptoms—chills, rapid breathing.

Endemic, Epidemic, Pandemic

• Endemic: Constantly present in a population (e.g., common cold).

• Epidemic: Sudden increase in cases in a region (e.g., seasonal influenza).

• Pandemic: Global epidemic (e.g., COVID-19).

Types of Bacterial Infections

• Local: Confined to small area (e.g., abscess).

• Systemic: Spread throughout body (e.g., measles).

• Focal: Local origin, spreads to other sites.

• Sepsis/Septicemia: Microbes/toxins in blood.

• Bacteremia/Toxemia: Bacteria/toxins in blood.

• Primary/Secondary: Initial vs. subsequent infection.

• Asymptomatic: No symptoms, but pathogen present.

Herd Immunity

• Occurs when enough individuals are immune (via vaccination or infection) to prevent disease spread.

• Protects vulnerable populations (e.g., infants, immunocompromised).

Predisposing Factors

• Nutrition: Malnutrition increases risk.

• Sex: Some infections more common in one sex.

• Genetics: Inherited disorders affect susceptibility.

• Climate: Seasonal changes affect transmission.

• Age: Young and elderly more susceptible.

Stages of Disease

1. Incubation Period: Time between infection and symptoms.

2. Prodromal Period: Mild symptoms appear.

3. Period of Illness: Most severe symptoms.

4. Period of Decline: Symptoms subside.

5. Period of Convalescence: Recovery and return to normal.

Reservoirs of Infection

• Human: Symptomatic or asymptomatic carriers.

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

• Nonliving: Soil, water (e.g., Legionella in water systems).

Vectors and Transmission

• Vectors: Organisms (often arthropods) that transmit pathogens.

• Mechanical Transmission: Passive transfer (e.g., flies carrying pathogens on feet).

• Biological Transmission: Pathogen reproduces in vector (e.g., mosquito transmits malaria).

Types of Disease Transmission

• Contact: Direct (person-to-person), indirect (fomites), droplet (cough/sneeze).

• Vehicle: Airborne, waterborne, foodborne.

• Vector: Mechanical or biological.

Healthcare-Associated Infections (HAIs)

• Sources: Hospital environment, compromised hosts, chain of transmission.

• Prevention: Sterilization, infection control, antimicrobial stewardship.

Microbial Mechanisms of Pathogenicity

Skin as a Barrier and Microbial Entry

• Physical Barrier: Keratinized, tightly packed cells resist invasion.

• Dryness and Acidic Secretions: Inhibit microbial growth.

• Entry Points: Breaks in skin, hair follicles, sweat ducts, parenteral route (punctures/injections).

ID50 and LD50

• ID50 (Infectious Dose 50): Number of microbes needed to infect 50% of a population.

• LD50 (Lethal Dose 50): Amount of toxin required to kill 50% of a population.

Formula (generalized):

$\mathrm{ID}_{50} = \text{Dose at which 50\% of subjects are infected}$

$\mathrm{LD}_{50} = \text{Dose at which 50\% of subjects die}$

Adhesins and Ligands

• Adhesins/Ligands: Surface molecules on pathogens that bind to host cell receptors, facilitating attachment.

• Examples: Streptococcus mutans (glycocalyx), E. coli (fimbriae), Neisseria gonorrhoeae (fimbriae), influenza virus (HA spike).

Bacterial Evasion of Host Immunity

• Capsules: Prevent phagocytosis (e.g., Streptococcus pneumoniae).

• Cell Wall Components: M protein, mycolic acid resist immune attack.

• Enzymes: Kinases, hyaluronidase, collagenase aid spread.

• Antigenic Variation: Surface antigen changes evade antibodies.

• Biofilms: EPS matrix protects from phagocytes.

Direct Damage by Bacteria

• Utilize host nutrients, produce waste, cause cell rupture.

• Induce host cell engulfment, penetrate cells, or produce toxins.

Endotoxins vs. Exotoxins

Feature	Exotoxins	Endotoxins
Source	Mostly Gram-positive bacteria	Gram-negative bacteria
Chemical Nature	Protein	Lipid A (LPS)
Release	Secreted during growth	Released upon cell death
Effect	Specific, potent	Systemic (fever, shock)
Example	Botulinum toxin	Salmonella endotoxin

Cytopathic Effects of Viruses

• Cytocidal: Cell death.

• Noncytocidal: Cell damage without death.

• Disruption of cell junctions, cytokine storm, inhibition of synthesis, lysosomal enzyme release, chromosomal changes.

Pathogenicity of Protozoa and Parasites

• Cyst Formation: Survival outside host.

• Cell Invasion: Intracellular reproduction (e.g., Plasmodium).

• Attachment: Specialized structures (e.g., Giardia).

• Antigenic Variation: Frequent surface antigen changes (e.g., Trypanosoma).

Additional info: Where details were brief or implied, academic context was added for clarity and completeness, such as expanded definitions, examples, and tables for comparison.