Exam 3 Micro

1:

• Basic Building Blocks of a Virus: Genome, virus structure, host cell tropism, hijacking of host machinery, host immune response, disease outcome, transmission, available vaccines and therapeutics.

• Benefits of Virus Particle Structure: Protection of nucleic acid, specificity in host cell interaction, genome delivery.

• Basic Steps in Virus Replication Cycle: Attachment/Entry, Replication/Transcription, Virion Assembly, Virion Release.

• How a Plaque Assay Works: Plaque-forming assays quantify cytotoxic viruses to measure virus neutralization. Plaque Reduction Neutralization Assay.

• pfu: Plaque forming units: Measure of infectious virus particles.

• MOI: Multiplicity of infection: Average number of virus particles infecting each cell. Multiplicity of infection (moi) = $\frac{Plaque forming units (pfu) of virus used for infection}{number of cells}$

• HBV and HDV Relationship: HDV requires HBV for transmission. HBV vaccine protects against Hepatitis D.

• Hepatitis Viruses with Vaccines: HAV, HBV, HDV (HBV vaccine works on HDV).

• Hepatitis Viruses with Treatments: HCV (Treatment available, no vaccine), HBV (Interferon alpha, Nucleoside/nucleotide analogs).

• Hepatitis Virus Transmission Routes: HAV

2:

The surface proteins of influenza are Hemagglutinin (HA) and Neuraminidase (NA). HA is responsible for attachment and membrane fusion by binding to sialic acid receptors on host cells. NA is responsible for viral release and spread by breaking down mucins.

Antigenic drift is caused by point mutations in the HA gene due to error-prone RNA polymerase, which requires new vaccines yearly. Antigenic shift is the reassortment of HA and NA genes, which leads to novel antigenic properties and potential pandemics.

Orthomyxoviruses have a segmented (-) RNA genome, which allows for gene reassortment. Paramyxoviruses have a non-segmented (-) RNA genome and use a single promoter model for transcription called Transcriptional Polarity.

R_0 or Basic Reproductive Number, is the average number of new infections that a single infected individual will cause in a population.

3:

• Papillomavirus Life Cycle and Epidermal Differentiation: Papillomavirus infects basal cells, establishes and maintains its genome, induces proliferation via E6/E7 proteins, amplifies its genome, expresses late genes, packages mature virions, and releases the virus. This cycle is coordinated with epidermal differentiation because the virus must infect basal cells (actively dividing) as it cannot infect differentiated cells in the spinous, granular, or cornified layers.

• Proteins Underlying Papillomavirus Cancer Development: The two key proteins are E6 and E7. E6 degrades p53, preventing cell cycle arrest and suppressing apoptosis. E7 degrades pRb, immortalizing epidermal cells and causing genome instability which causes cancer.

• Advantage for the Virus: The virus benefits by creating an environment conducive to its replication and spread. By deregulating the cell cycle and preventing apoptosis, the virus ensures the host cells continue to produce viral particles. Through cancer, it promotes long-term survival and propagation.

• Polyomavirus (JC and BK) Spread: JC/BK viruses spread through inoculation of the respiratory tract, multiply there, and cause primary viremia. They multiply in the kidneys and become latent there indefinitely in immunocompetent individuals, leading to transient secondary viremia. In immunodeficient individuals, BK virus multiplies in the urinary tract, causing viruria and possible hemorrhagic cystitis, while JC virus viremia can cause progressive multifocal leukoencephalopathy (PML) in the CNS.

• Virobiota: The virobiota consists of viruses in the human microbiome. They are potentially important to human health because they can provide evolutionary advantages to bacteria, protect mucosal barriers from pathogens, perturb our immune system, and integrate new genetic material into our cells. Additionally, master gene regulators like p53 and pRb may have originated from endogenous retrovirus genes.

4:

Human Retroviruses

• Lymphotropic: HTLV 1, 2, and 3.

• Immunodeficiency: HIV-1 and -2.

• Lentiviruses: Infect humans, cows, cats, monkeys, and horses.

HIV

• Human Immunodeficiency Virus.

HIV Virion Components

• Envelope proteins (gp120/gp41).

• Matrix.

• Capsid.

• 2 RNA molecules (positive polarity).

• Nucleocapsid.

• Integrase.

• Reverse Transcriptase.

• Protease.

HIV Genome

• 9 genes encoding 15 proteins.

• Long Terminal Repeat (LTR): promoters, important for integration.

• Gag: structural proteins.

• Pol: enzymes (reverse transcriptase, protease, integrase).

• Env: envelope proteins (gp120 and gp41).

• Additional genes: accessory and regulatory proteins.

HIV Life Cycle

1. Envelop proteins bind to the CD4 receptor.

2. Fusion.

3. Reverse transcription (RNA to DNA).

4. Integration.

5. Transcription/Translation.

6. Assembly.

7. Release/Budding.

   • Receptor/Coreceptors: gp120 binds to CD4 receptor, then to coreceptor.

   • Enzymes:

     • Reverse transcriptase: RNA to DNA.

     • Integrase: integrates viral DNA into host DNA.

     • Protease: processes viral proteins for maturation.

HIV Entry

1. gp120 binds to cell surface.

2. gp120 binds to CD4 receptor.

3. Conformation changes allow gp120 to bind to coreceptor.

4. Conformational changes in gp41 expose fusion peptide.

HIV Reverse Transcription

• Viral core delivered to cytoplasm.

• Process of converting viral RNA into DNA.

How HIV is Transmitted

• Birth, heterosexual/homosexual sex, blood products

5:

1. Poxvirus vs. Herpesvirus Replication

   • Poxviruses: Large, dsDNA viruses that replicate in the cytoplasm.

   • Herpesviruses: dsDNA viruses that replicate in the nucleus, utilizing immediate early, early, and late phases of transcription.

2. Smallpox History

   • Smallpox (Variola virus): Eradicated in 1980 due to effective vaccine, obvious symptoms, lack of asymptomatic cases, and spread only via close contact.

3. Vaccine Status: Poxviruses and Herpesviruses

   • Smallpox: Effective vaccine (eradicated).

   • Varicella: Live attenuated vaccine (Varivax).

   • Zoster: Recombinant vaccine (Shingrix).

   • Other herpesviruses (HSV, EBV, CMV): No vaccines available.

4. Herpesvirus Genome

   • Double-stranded, linear DNA genomes (70-200 proteins).

5. Herpesvirus Latency and Reactivation

   • Establish latency as episomes (naked, circular DNA) in sensory ganglia.

   • Reactivation: Triggered by UV light, infections, stress, or immunosuppression.

   • Latency-associated transcripts (LATs): Silence lytic genes during latency.

6. Herpesvirus Latency vs. HIV Latency

   • Herpesviruses: Latent as episomes.

   • HIV: Integrates its genome into the host cell DNA.

7. Herpesviruses by Name, Number, and Disease

   • HSV-1 (HHV-1): Oral/ocular herpes, keratitis, encephalitis.

   • HSV-2 (HHV-2): Genital herpes.

   • VZV (HHV-3): Chickenpox, shingles.

   • EBV (HHV-4): Infectious mononucleosis, Burkitt

6:

• The structure of small gastrointestinal viruses is important for several reasons:

  • Protection: It protects the fragile nucleic acid genome against physical, chemical, or enzymatic damage.

  • Specificity: It facilitates recognition and interaction with host cells and aids in the delivery of the viral genome into the cell.

• Norovirus: Causes acute gastroenteritis with violent diarrhea and vomiting; severe dehydration can lead to death; shedding continues for weeks after symptoms are gone; extremely contagious. Rotavirus: Causes rotaviral gastroenteritis with nausea, vomiting, and runny diarrhea; a vaccine is available and effective.

• Polio is dangerous because it can lead to paralytic poliomyelitis, infecting the spinal cord and motor cortex, resulting in varying degrees of paralysis.

• Rotavirus: is very deadly to children. Vaccination: 80-100% effective.

• A viroplasm is an area in the cell devoted to viral replication; it's a virus replication factory or inclusion body.

7:

Zoonosis

• Diseases transmissible from vertebrate animals to humans.

Emerging Virus

• Newly discovered or increasing in incidence/virulence/mortality.

• Can expand host range.

• Zoonosis: transmission from animals to humans.

• Lack of pre-existing immunity in the new species poses a public health threat.

Why Ebola Is Dangerous

• Can replicate in multiple cell types (monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, liver cells, adrenal cortical cells).

Why Zika Virus Is Dangerous to the Unborn Child

• Placenta shuttles ZIKV to fetus, causing microcephaly.

• Potential Routes to Developing Fetus:

  • Placental route (first trimester)

  • Route across the amniotic sac (second trimester).

• Symptoms of Congenital Zika Syndrome: microcephaly, decreased brain tissue, eye damage, extreme muscle tone, and limited range of motion.

Difficulty in Tracing Virus Origins

• Origin tracing requires further investigation into the food chain and farmed wild animals.

• All hypotheses regarding the