Lecture 10

Question 1

How does a virion enter the host?

Question 2

What is the initial host response?

Answer 2

(does it recognize the infection and get rid of it immediately, or does it stay hidden)?

Question 3

Where does the primary infection occur?

Answer 3

(What are the receptors on cells that the virus requires to enter, is it near where the host became exposed to the virus?)

Question 4

How does the infection spread in the host?

Question 5

What organs and tissues are infected?

Question 6

Is the infection cleared from the host or is a persistent infection established?

Question 7

How is the virus transmitted to other hosts?

Question 8

What does the term virulence mean?

Answer 8

The virulence of a virus indicates how effectively it can cause disease or harm in its host.

Question 9

What are some reasons that the interaction of the virus with target tissues is important in viral pathogenesis?

Answer 9

• Access of the virus to target tissues
• Stability of the virus in the body (e.g., temperature, acid, and bile in the GI tract)
• Capacity to establish viremia (presence of the virus in the bloodstream)
• Target tissue characteristics, such as the presence of appropriate virus receptors.

Question 10

Define viremia and its significance in viral pathogenesis.

Answer 10

Viremia = virus particles in the bloodstream.

The capacity of a virus to establish viremia is critical in viral pathogenesis as it enables the virus to spread throughout the body via the circulatory system, potentially infecting multiple organs and tissues.

Question 11

What are some aspects of the host response to viral infection?

Answer 11

Intrinsic cellular antiviral defenses (Pre-existing features or factors that are present in cells that are capable of targeting or inhibiting virus replication)

Innate immune responses. (Rapid responses, tend not to be specific (globally antiviral)

Acquired immune responses. (Very specific, immunological memory)

Viral immune escape mechanisms.

Question 11

What are some additional determinants of viral pathogenesis related to the ability of infection to kill cells and other factors?

Answer 11

• Efficiency of virus replication in the cell, influenced by factors like optimal temperature and cell permissivity.
• Presence of cytotoxic viral proteins.
• Inhibition of macromolecular synthesis.
• Production of viral proteins and structures (e.g., inclusion bodies and replication factories).
• Alteration of cell metabolism.

Question 12

What does it mean when a cells is susceptible, but not permissive?

Answer 12

Many cells can be susceptible (allow the virus in; which can be determined by factors on the surface of the cell such as receptors), but not permissive (meaning it cant replicate in the cell)

Question 13

What is immunopathology in the context of viral infections?

Answer 13

Immunopathology refers to the disease caused by the host’s immune response to viral infection.

Question 14

How do interferon and other cytokines contribute to immunopathology?

Answer 14

Interferon and other cytokines can induce systemic symptoms such as fever, chills, nausea, and malaise as part of the host’s immune response to viral infection.

Question 15

How do T-cell responses contribute to immunopathology?

Answer 15

T-cell responses can lead to the release of cytokines, activating nonspecific effector cells like neutrophils.

Neutrophils are phagocytic cells, but they also produce reactive oxygen species that can damage tissue, resulting in more inflammation and swelling.

Question 16

How does the antibody response contribute to immunopathology?

Answer 16

The antibody response can contribute to immunopathology through various mechanisms.

Antibodies are multivalent, meaning they have at least two sites on them that can bind to antigens.

This allows them to cause crosslinking with large complexes (immune complexes), which can lead to conditions like glomerulonephritis, where the kidneys are inflamed due to the clogging of blood vessels by immune complexes.

Question 17

How do complement proteins contribute to immunopathology?

Answer 17

Complement proteins in the blood can recognize antibodies bound to membranes and form attack complexes.

This process eventually leads to the rupturing of cells, releasing cytoplasmic contents, which serves as a potent danger signal to the immune system, causing inflammation. Immune cells are then attracted to the site of inflammation.

Question 18

What factors contribute to the virulence of a virus?

Answer 18

Virulence, or the severity of a viral infection, is influenced by several factors. Among viral factors are the amount of virus present (dose), the pathway through which it enters the body, its preference for specific tissues (tissue tropism), and the genetic makeup of the virus, particularly genes affecting its ability to bind to host cells.

Question 19

What host-related factors affect viral pathogenesis?

Answer 19

Host factors influencing viral pathogenesis include
- age (with the young and elderly being more susceptible)
- immune status (e.g., immunocompromised individuals)
- host genotype (variation in cell receptor structure)
- nutritional status (impacting immune response quality)
- previous infections (which can alter immune system responses and availability of immune cell types).

Question 20

What critical assumptions underlie models of virus-host interactions?

Answer 20

• Common themes and strategies exist in viral-host interactions despite diverse virus types.
• Viruses must maintain stability in the environment before encountering a susceptible host.
• Successful infection requires entry into a susceptible host and subsequent replication.
• Viruses must overcome obstacles at each stage of infection to progress further.

Question 21

What are the obligatory steps for infectious microorganisms?

Answer 21

1. Attachment and entry into the body (infection): This step involves evading the host’s natural protective and cleansing mechanisms, such as mucus, blinking, tears, and dead skin, to successfully enter the body.
2. Local or general spread in the body: After entry, the microorganism must evade immediate local defenses and natural barriers to spread, like mucus and swallowing, to establish infection in various body regions.
3. Multiplication: Once established, the microorganism must multiply, with many offspring dying in the host or during transmission to new hosts.
4. Evasion of host defenses: Throughout the infection, the microorganism must evade the host’s phagocytic and immune defenses long enough to complete its life cycle.
5. Shedding (exit) from the body (transmission): To ensure spread to new hosts, the microorganism must exit the body in sufficient quantities and at appropriate sites, often through mechanisms like coughing or diarrhea.
6. Cause damage in the host (pathology, disease): While not always necessary, many infections result in damage to the host, leading to pathology and disease. However, some infections can be asymptomatic.

Question 22

What some physical barriers to the initiation of a virus infection?

Answer 22

Skin: with secretions and a keratinized, dead layer of cells.

Conjunctiva: protected by tears and blinking, which mechanically wash the surface of the eye.

Respiratory tract: with secretions, a mucociliary elevator, and immune cells.

Oral cavity: where copious amounts of saliva are produced and swallowed.

GI tract: protected by secretions and the acidic pH of the stomach. Other innate immune defenses also play a role.

Question 23

What is the function of the mucociliary elevator in the respiratory tract?

Answer 23

The mucociliary elevator consists of ciliated cells in the respiratory tract that move mucus upward, trapping pathogens and debris, which can then be swallowed and destroyed in the acidic pH of the stomach.

Question 24

What are Langerhans cells, and what happens if they are infected?

Answer 24

Langerhans cells are dendritic cells found in the skin that are phagocytic and function as antigen-presenting cells. They present antigens to cells of the immune system to initiate an adaptive immune response.

Some viruses can infect Langerhans cells, activating them to infect immune cells in the lymph nodes instead of presenting antigens. This can lead to the dissemination of virally infected cells throughout the body.

Question 25

What are Peyer’s patches and M cells, and what is their role in the immune system?

Answer 25

Peyer’s patches are lymphoid tissue regions in the intestine, resembling elongated thickenings of the intestinal epithelium.

M cells (microfold cells) are continuously sampling antigens from the intestinal lumen and transporting them to the basolateral membrane and presenting them to immune cells in the Peyer’s patches.

This mechanism aids in immune surveillance but can also be exploited by viruses to gain entry into the host, posing a risk to health.

Question 26

What are mechanisms for the spread of viruses from the blood into tissues?

Answer 26

Infection of endothelial cells: Viruses can infect endothelial cells lining blood vessels, leading to replication within these cells and subsequent shedding of the virus into the surrounding tissues. Hemorrhagic viruses, in particular, are known to cause endothelial cell death, which can lead to the release of virus particles into the tissues.

Transcytosis: Endothelial cells can transport viruses across the endothelium via transcytosis, allowing them to move from the blood into the tissues.

Diapedesis: Viruses can also move from the blood into tissues by squeezing between endothelial cells and migrating into the tissues, a process known as diapedesis.

Question 27

What are the stages in acute viremia (describe each)

Answer 27

Passive viremia: This occurs as a consequence of experimental infection, often through direct injection of the virus into the bloodstream. In this case, the virus is introduced directly into the bloodstream, bypassing the initial replication within the host.

Primary viremia: This stage occurs when the initial infection takes place. The virus infects immune cells in the tissues, which then travel to the lymph nodes. In the lymph nodes, the infection spreads to other cells, leading to an increase in the number of infected cells.

Secondary viremia: This stage involves a significant increase in viral load. Infected cells leave the lymph nodes and migrate to other tissues. Here, the virus undergoes further replication and amplification before entering the bloodstream again, leading to a higher concentration of virus in the blood.

Question 28

What are the modes of transmission of infectious agents?

Answer 28

Human-human:
- Respiratory or salivary spread
- Fecal-oral spread
- Venereal spread

Zoonoses: Infections acquired from animals, which can be controlled in humans by controlling animal infections.
- Vector: Transmission through biting arthropods.
- Vertebrate reservoir: Maintenance of the infectious agent in animal populations.
- Vector-vertebrate reservoir: Combination of transmission through biting arthropods and maintenance of the infectious agent in animal populations.

Question 29

What is disease?

Answer 29

1. Disease is an impairment of health or a condition of abnormal functioning.
2. It is a pathological condition of a part, organ, or system of an organism resulting from various causes, such as infection, genetic defect, or environmental stress, and characterized by an identifiable group of signs or symptoms.

Question 30

T or F: One disease or symptom cannot be caused by more than one type of virus

Answer 30

F: of course

Question 31

T or F: A particular virus can cause more than one type of disease

Answer 31

T

Question 32

What are the types of virus infections?

Answer 32

Acute infection: Successful completion of all stages of viral replication may result in disease, characterized by a rapid onset of symptoms. Examples include influenza A virus and rhinovirus.

Chronic/persistent or latent infection: Failure to complete all stages of viral replication results in either abortive or nonproductive infection. Examples include hepatitis B virus and herpes simplex 1, where the virus remains in the body for extended periods, occasionally causing recurrent symptoms.

Slow virus diseases: These infections involve a slow development of symptoms over time. Examples include measles leading to subacute sclerosing panencephalitis and HIV, which progresses slowly to AIDS.

Question 33

What is the difference between chronic and slow virus diseases?

Answer 33

Chronic Virus Diseases:

• Chronic virus diseases involve the persistence of the virus in the body over an extended period.
• These infections may exhibit periodic or recurrent symptoms.
• Examples include hepatitis B virus and herpes simplex virus 1.
• In chronic infections, the virus remains active and can potentially cause symptoms or complications throughout the individual’s life.

Slow Virus Diseases:

• Slow virus diseases are characterized by a gradual onset and slow progression of symptoms over an extended period, often spanning months or years.
• Symptoms may not be apparent until the disease has progressed significantly.
• Examples include subacute sclerosing panencephalitis (SSPE) associated with measles virus and human immunodeficiency virus (HIV).
• In slow virus diseases, the virus replicates slowly and progressively damages the host’s tissues or immune system, leading to the gradual development of symptoms and disease progression.

Question 34

What characterizes acute infections?

Answer 34

Acute infections are characterized by the rapid production of virus followed by the rapid resolution and clearing of the infection by the host.

These infections typically have a short duration and are often associated with a rapid onset of symptoms. Many symptoms of acute infection (e.g. fever, malaise, aches, nausea) are due to a robust host immune response.
* e.g. the interferon response

Question 35

What are latent infections, and what is an example?

Answer 35

• Latent infections are characterized by the persistence of the virus in a dormant state within the host cell. (e.g. herpes simplex virus type 1 (HSV-1) and varicella zooster virus (VZV))
• During latency, the virus genome persists in the nucleus of the neuron, with only a small subset of genes being expressed.
• Reactivation from latency triggers virus replication and shedding, often resulting in characteristic disease symptoms.

Question 36

What virus is known to cause lifelong infections and why?

Answer 36

Herpesviruses are known to cause lifelong infections due to their ability to establish latency and reactivate periodically.

Question 37

How does Varicella Zoster Virus (VZV) work (Very briefly)?

Answer 37

VZV infects T cells and modifies their program, transforming them into skin-homing T-cells. These T-cells migrate to the skin, shedding virus onto skin cells, leading to the formation of blisters characteristic of chickenpox.