Biomedical Sciences: Viral Pathogenesis and Immunity (Lecture 8; Exam 2)

What are viral factors?

• Virulence of virus

• Viral dose

Host Immune Status

• Newborns

• Immune-compromised

• Pregnant women

• Unvaccinated

When do viruses cause disease?

The virus must first successfully infect a cell.

Infection means entering a cell, replicating and releasing infectious progeny.

What are the phases of viral disease?

1. Contagion

2. Acquisition

3. Primary site replication

4. Secondary site replication

5. Target tissue

How do viruses cause disease?

• Destroy or disrupt normal tissue function

• Induce destructive immune responses

• Suppress immunity

• Cause cancer

What is cytopathogenesis?

The direct damage from viruses.

What is immunopathogenesis?

The indirect damage resulting from immune responses.

Clinical signs and symptoms primarily result of host response to infection.

What is immunosuppression?

Suppresses immunity.

Cytopathogenesis:

• Lytic infections directly kill cells.

• Destroy or disrupt normal tissue function.

• Shutdown of macromolecule synthesis.

• Induce apoptosis

What is syncytia formation?

A process where cell-cell fusion forms multinucleated giant cells.

• Allows cell-cell spread, escaping antibody detection

• May be fragile and susceptible to lysis

What is oncogenesis?

Causes cancer.

What are inclusion bodies?

Abnormal clumps of protein or viral particles that build up inside a cell’s nucleus or cytoplasm during a viral infection.

• Stainable structures.

• Changes in membrane or chromosomal structures, sites of viral replication, accumulation of viral capsids.

Immunopathology:

• CD8+ T cell mediated

• CD4+ T cell mediated

• Antibody-mediated

• Interferon production

What do CD8+ T cells do?

Act as cytotoxic killer cells that directly destroy virus-infected or cancerous cells.

What do CD4+ T cells do?

Act as helper cells that coordinate the overall immune response by signaling other cells.

What is interferon production?

The process where body cells synthesize and release protective signaling proteins (called interferons) when they detect harmful invadors like viruses.

What are Oncogenic Infections?

Certain DNA viruses and retroviruses establish persistent infections causing transformation or immortalization leading to cancer.

What do oncogenic infections do?

• Activate or provide growth stimulating genes

• Remove braking mechanisms that limit DNA synthesis and growth.

• Prevent apoptosis

• Encode oncogenes

• Stimulate chronic inflammation and repair

What needs to occur for a virus to infect a host?

• Enter an appropriate cell

• Use the cell’s machinery for replication

• Keep the host from recognizing and destroying the infected cell.

• Move to new cells or hosts.

What needs to be considered for a virus to infect a cell?

• Route of transmission

• Initial immune defense evasion

• Species, tissue, cell tropism

• Viral replication cycle

What is the MAIN determinant of transmission?

Presence or absence of an envelope.

What is contagion?

The transmission of a disease through direct or indirect contact.

What are examples of routes of transmission?

• Respiratory

• Fecal-oral route

• Contact

• Zoonoses (viruses shared by animals or insects and humans)

• Transmission via blood

• Sexual contact

• Maternal-neonatal transmission

• Genetic

What genome does SARS-CoV-2 have?

(+) ssRNA, Enveloped

What is phase 2 of infection?

Acquisition.

What are the three conditions a virus must meet to gain access to cells, establish infection and begin replicating?

1. Quantity of Virus

2. Availability of target cells

3. Local host anti-viral defense systems must be absent, initially ineffective or subverted.

What does an infectious dose mean?

Amount or virus needed to establish an infection.

A virus must be present in high enough concentrations to initiate infection.

Factors that promote transmission?

• Stability of virus in the environment

• Virus shed in aerosols/secretions

• Ability to spread before symptoms (Pre-symptomatic Transmission)

  • Incidence of asymptomatic infections

• Ineffective immune control of reinfection or recurrence

What is pre-symptomatic transmission?

The spread of an infection from a person who has the virus and is contagious, but has not yet developed symptoms.

What is the third phase of infection?

Replication.

Virus begins replicating in cells close to the initial infection site.

Incubation Period

Time from exposure to signs and/or symptoms occurring.

Phase of infection where virus is replicating but has not reached the target tissue or induced sufficient damage to cause disease.

True/False: Innate immune responses are continuing at the time of replication.

True.

What is a short incubation period?

Occurs when the target tissue is the primary site of infection and produces the characteristic symptoms of the disease.

What is a long incubation period?

Occurs when the virus must spread to other sites and be amplified before reaching the target tissue.

(Symptoms often caused by immunopathology)

What are the phases of Viral Disease?

1). Contagion

2). Acquisition

3). Primary Site Replication

4). Secondary Site Replication

5). Target Tissue

Which cell of the adaptive immune system DIRECTLY kills virally infected cells?

CD8+ T Cells.

What do CD4+ T Cells do?

Coordinate adaptive and innate responses to infection.

(Provide “help” to macrophages, B cells)

What do CD8+ T cells do?

Kill infected cells (apoptosis).

What are CD8+ T cells required for?

Required for lysis of cells infected with non-lytic viruses and enveloped viruses.

What do Natural Killer Cells do?

Detect lack of MHC I to kill “unusual cells”.

What are Cytokines? (Interferon)

Small proteins released by cells that act as chemical messengers to control immune responses and cell communication.

What do Antibodies do?

Prevent reinfection.

• Limits spread within host and to new hosts

• May help kill infected cells

• Induced by most protective vaccines

• Neutralize free, extracellular virus

True/False: Interferons are cytokines.

True.

True/False: Every viral infection triggers interferon production.

True.

What are clinical effects of interferons?

Classic “flu-like symptoms”.

• Malaise

• Myalgia

• Chills

• Fever

What are antiviral actions of interferons?

• Initiate antiviral state in cells

• Block viral protein synthesis in infected cells

• Inhibit cell growth

What are immunomodulatory actions of interferons?

• Activate NK cells

• Activate macrophages

• Increase MHC expression (class I and class II)

• Enhances T-cell recognition of infected cells

Outcomes of Viral Infections at cellular level:

• Abortive infection

• Lytic infection

• Persistent infection

  • Chronic productive
    Latent infection

• Transforming infection

Abortive Infection

Failed infection; virus does not multiply.

Lytic Infection

Cell death.

Persistent Infection

Does not kill cell (non-lytic)

• Chronic Productive: Replication without cell death, makes new virus.

• Latent Infection: Presence of virus without virus production but with the potential for reactivation.

  • (Hides in cell)

Transforming Infection

Cancer causing.

Oncogenic: Immortalization of a cell

Acute Infection

• Asymptomatic (subclinical) infection

• Illness, viral clearance - Norovirus

  • (Full recovery)

• Illness, viral clearance - Polio

  • (Long-term effects on health)

• Death

Outcomes of Persistent Infection:

• Silent subclinical infection

• Slow progressive disease

• Intermittent reactivation

• Chronic replication

• Cancer

Characteristics of Localized Infection:

• May be acute or persistent

• Replicate at site of entery

• Usually short incubation period (days)

• Shedding to the exterior

• Little or no invasion of underlying tissues

• Viremia does not occur

Examples of localized infections:

• Oral/genital herpes simplex (usually)

• Respiratory infections

• Influenza

• Warts

Characteristics of Systemic infections:

• Blood-borne phase (viremia)

• Incubation period usually > 1 week

• Longer period of shedding

• Symptoms usually more pronounced and systemic

• Disseminated throughout the body via lymphatics and bloodstream.

• Ultimately may cause disease at some site distant from entry (if symptomatic)

Examples of Systemic Infections:

• Smallpox

• Measles

• Chickenpox

• HIV

True/False: Every viral infection triggers IFN production.

True.

Interferons are ____.

Cytokines.