How does a virion enter the host?
What is the initial host response?
(does it recognize the infection and get rid of it immediately, or does it stay hidden)?
Where does the primary infection occur?
(What are the receptors on cells that the virus requires to enter, is it near where the host became exposed to the virus?)
How does the infection spread in the host?
What organs and tissues are infected?
Is the infection cleared from the host or is a persistent infection established?
How is the virus transmitted to other hosts?
What does the term virulence mean?
The virulence of a virus indicates how effectively it can cause disease or harm in its host.
What are some reasons that the interaction of the virus with target tissues is important in viral pathogenesis?
- 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.
Define viremia and its significance in viral pathogenesis.
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.
What are some aspects of the host response to viral infection?
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.
What are some additional determinants of viral pathogenesis related to the ability of infection to kill cells and other factors?
- 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.
What does it mean when a cells is susceptible, but not permissive?
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)
What is immunopathology in the context of viral infections?
Immunopathology refers to the disease caused by the host’s immune response to viral infection.
How do interferon and other cytokines contribute to immunopathology?
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.
How do T-cell responses contribute to immunopathology?
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.
How does the antibody response contribute to immunopathology?
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.
How do complement proteins contribute to immunopathology?
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.
What factors contribute to the virulence of a virus?
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.
What host-related factors affect viral pathogenesis?
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).
What critical assumptions underlie models of virus-host interactions?
- 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.
What are the obligatory steps for infectious microorganisms?
- 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.
- 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.
- Multiplication: Once established, the microorganism must multiply, with many offspring dying in the host or during transmission to new hosts.
- 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.
- 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.
- 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.
What some physical barriers to the initiation of a virus infection?
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.
What is the function of the mucociliary elevator in the respiratory tract?
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.
