Pathogenesis of Viral Infections

Viral Entry & Spread - Gateway Invaders

• Portals of Entry: Resp. (Influenza), GI (Rotavirus), Skin (HPV), GU (HSV), Transplacental (Rubella).
• Key Steps:
  • Attachment: Viral ligand ↔ Host cell receptor. Defines tropism (e.g., HIV gp120 to CD4).
  • Penetration:
    • Direct Fusion (e.g., HIV, Measles) with cell membrane.
    • Endocytosis (e.g., Influenza, Adenovirus); pH-dependent uncoating.
  • Uncoating: Viral genome release.
• Spread:
  • Local: Cell-to-cell (syncytia: RSV, HIV); extracellular release.
  • Systemic:
    • Hematogenous (Viremia): Primary & secondary phases.

    ⭐ Viremia is the most common route for systemic viral dissemination.

    • Lymphatic: To nodes, then bloodstream.
    • Neural: Axonal transport (Rabies, HSV, Polio).

Cell Tropism & Damage - Target Lock Tactics

• Cell Tropism: Virus's selective affinity for specific host cells/tissues. 📌 Tropism = Susceptibility (receptors) + Permissivity (replication factors).
  • Key Determinants:
    • Host cell surface receptors (e.g., HIV gp120 & CD4).
    • Cellular factors for viral replication (e.g., transcription factors).
    • Physical accessibility, local environment (pH, temperature).
• Mechanisms of Cell Damage (Cytopathic Effects - CPE):
  • Direct Effects:
    • Inhibition of host protein, RNA, DNA synthesis.
    • Cell fusion (syncytia formation) e.g., Measles, RSV, HIV.
    • Inclusion bodies (e.g., Negri bodies - Rabies; Cowdry type A - HSV; Owl's eye - CMV).
    • Induction of apoptosis.
  • Indirect (Immune-Mediated) Damage:
    • Cytotoxic T-lymphocyte (CTL) killing of infected cells.

⭐ Some viruses encode anti-apoptosis proteins to prolong cell survival for maximal viral replication (e.g., Cowpox crmA protein).

Host Response & Evasion - Immune System Showdown

• Host Defenses:
  • Innate (Rapid):
    • Interferons ($IFN-\alpha/\beta$): Antiviral state.
    • NK cells: Kill infected cells (↓MHC-I).
    • Macrophages: Phagocytosis, Ag presentation.
  • Adaptive (Specific, Memory):
    • Humoral (B-cells → Abs): Neutralization, opsonization, ADCC.
    • Cellular (T-cells):
      • CTLs (CD8+): Lyse infected cells.
      • Th cells (CD4+): Coordinate response.
• Viral Evasion Mechanisms: 📌 "HIDE & SEEK"
  • Hiding (Latency): Herpesviruses.
  • Interfering MHC presentation: Adeno, CMV (↓MHC-I).
  • Decoying: Virokines/Viroceptors.
  • Evolving (Antigenic variation): Influenza, HIV.
  • Suppressing apoptosis.
  • Encoding IFN antagonists: HCV.
  • Escaping Ab neutralization.
  • Killing immune cells: HIV (CD4+).

⭐ CMV (US2, US3, US6, US11) & Adenovirus (E3/19K) downregulate MHC-I to evade CTL detection.

Infection Patterns & Outcomes - Viral Legacy

• Acute Infections: Rapid onset, short duration; virus cleared. E.g., Influenza, Rotavirus.
• Persistent Infections: Virus evades clearance.
  • Chronic: Continuous viral shedding; long-term disease. E.g., HBV, HCV, HIV.
    • Organ damage (cirrhosis, AIDS).
  • Latent: Dormant virus, reactivates periodically. E.g., Herpesviruses (HSV, VZV), CMV.
  • Slow: Long incubation; progressive, fatal. E.g., Measles (SSPE), Prions (CJD).
• Key Outcomes:
  • Oncogenesis (HPV, EBV, HTLV-1, HBV, HCV).
  • Immunopathology (host response damage).
  • Congenital (Rubella, CMV, Zika). 📌 Rubella, CMV, Zika: key viral teratogens.

⭐ Measles virus can cause Subacute Sclerosing Panencephalitis (SSPE), a rare, progressive, fatal neurological disease years after initial infection.

High‑Yield Points - ⚡ Biggest Takeaways

• Viral entry (e.g., fusion, endocytosis) and tissue tropism are critical initial steps.
• Cell injury results from direct cytopathic effects (CPE) or host immune-mediated damage.
• Key infection patterns include acute, chronic (persistent), and latent infections.
• Host immune responses (IFNs, CTLs) combat viruses but can cause immunopathology.
• Viruses utilize immune evasion mechanisms such as antigenic variation and latency.
• Certain viruses possess oncogenic potential, leading to cancer.
• Viremia (virus in blood) is crucial for systemic dissemination.