Viral Pathogenesis: Entry, Spread, and Damage

• Viral pathogenesis is how viruses cause disease within a host
• A complex interaction between the virus and the host's immune system determines the severity and nature of the disease

Viral Entry

• Viruses require host entry to initiate infection
• Entry routes: respiratory tract, gastrointestinal tract, skin, and mucous membranes
• Some viruses need specific host cell receptors for attachment and entry
• Others use more general entry mechanisms

Viral Spread

• After entering, viruses spread locally or systemically
• Local spread: replication and infection of nearby cells
• Systemic spread: dissemination to distant organs/tissues via bloodstream/lymphatic system
• Viral tropism directs spread patterns and resulting disease

Cellular and Tissue Damage

• Viruses can damage cells/tissues through specific mechanisms
• Cytopathic effects (CPEs) are direct impacts of viral replication on host cells
• CPEs lead to cell death or dysfunction
• Immune-mediated damage occurs when the host's immune response targets virus-infected cells, causing inflammation and injury

Host Immune Response

• The host immune response greatly determines viral pathogenesis
• Innate immunity gives an immediate, non-specific defense
• Innate immunity defenses: interferon production and natural killer (NK) cell activity
• Adaptive immunity (antibodies and T cells) offers a more specific, lasting defense
• Adaptive immunity can also lead to immunopathology

Viral Evasion Strategies

• Viruses have developed strategies to evade the host immune response
• Antigenic variation (mutation and recombination) helps viruses escape antibody neutralization
• Some viruses suppress or interfere with interferon signaling, inhibiting the antiviral state
• Latency (persistent infection without active replication) helps viruses evade immune detection and clearance

Factors Influencing Viral Pathogenesis

• Viral factors, like virulence genes and replication efficiency, affect disease severity
• Host factors, including age, genetics, immune status, and co-infections, also affect viral infection outcomes
• Environmental factors (stressors or pollutants) can change the host's susceptibility to viral disease

Mechanisms of Viral Persistence

• Some viruses cause persistent infections via latency or chronic replication
• Latency is the maintenance of viral DNA within host cells without active replication
• Latency lets the virus evade immune detection
• Chronic replication is continuous/intermittent viral replication
• Chronic replication is often linked to chronic inflammation and tissue damage

Examples of Viral Pathogenesis

• Influenza virus causes respiratory illness through direct cytopathic effects and immune-mediated damage
• HIV infects, destroys CD4+ T cells, causing immunodeficiency and opportunistic infections
• Hepatitis B virus causes chronic liver infection
• Chronic liver infection leads to cirrhosis and hepatocellular carcinoma
• Herpes simplex virus establishes latency in sensory neurons, causing recurrent outbreaks of cold sores or genital herpes

Measurement of Viral Pathogenesis

• Viral load measurement reveals the quantity of virus present in an infected individual
• Measurements of immune cell counts (CD4+ T cell count for HIV) help assess the virus' impact on the immune system
• Cytokine profiling reveals the balance of immune activation and suppression in response to viral infection
• Cytokine levels give insights into disease mechanisms and potential therapeutic targets

Animal Models of Viral Pathogenesis

• Animal models aid study of viral pathogenesis and testing of antiviral therapies
• Commonly-used models of human viral infections: mice, ferrets, and non-human primates
• Transgenic and knockout mice help researchers study the role of specific host genes in viral pathogenesis
• Animal models help assess the efficacy of novel therapeutics/vaccine candidates