MECHANISM OF VIRAL INFECTION, SPREAD, AND TRANSMISSION

• Virus life cycle steps that shape pathogenesis

  1. Entry of the virus into the body

  2. Local replication in susceptible cells (tissue tropism, modulate the host innate immune response)

  3. Dissemination and spread to secondary tissues and target organs

  4. Secondary replication in susceptible cells

  5. Shedding of the virus into the environment

  6. Transmission to new host
• Viruses must gain entry into their host's body, replicate, and spread, either on specific organs or systematically
• To survive in nature, viruses must be transmitted, i.e., they must be shed with secretions or excretions into the environment, be taken up by a host or a vector, or be passed from mother to offspring
• The Respiratory Tract is the most common entryway of viruses towards the body
• Cells lining up the mucosa of the respiratory tract can serve as a site for replication of viruses
• Most inhaled virions are trapped in mucus, carried by the ciliary action of the cells towards the pharynx, and then swallowed or coughed out
• Smaller viruses (<5 µm) are usually inhaled directly into the lungs, to where alveolar macrophages ingest them
• Viruses aim to evade the host's natural protective and cleansing mechanisms
• Respiratory viruses

  • Rhino-, Calici-, Paramyxo-, Rubela-, Pneumo-, Orthomyxo-, & Adeno-viruses
• Many viruses are acquired through ingestion
• GI tracts tend to have mucus for protection
• Enzymes and other secretions of the GI tract (acids) can inhibit some viruses from infecting the cells
• Viruses that cause intestinal infection

  • Rotaviruses, Caliciviruses, Enteroviruses
• Viruses that are labile to acid and bile like bovine, porcine, and murine coronaviruses use buffers (such as milk) to pass through the stomach
• Some Corona- and Rota-viruses become more activated at exposure to enzymes
• The Skin's outer layer consists of keratinized cells, providing a tough barrier to the entry of viruses
• Cuts, punctures, abrasions, or wounds expose deep epidermal layers which can be an entryway for viruses
• Papillomaviruses can take advantage of openings in the skin and proliferate locally
• Deeper cuts introduce the virus to the dermis, the layer with rich blood supply, leading to viremia or generalized infection
• Viruses can be introduced into the skin through arthropod bites
• Sometimes, bites of larger animals can introduce viruses as well
• Viruses can be iatrogenically introduced into the skin as a hazard of
• Routes of entry of viruses through the Skin

  1. Introduction through arthropod bites

  2. Introduction through larger bites
• Routes of entry of viruses through the Skin

  Iatrogenic introduction of the virus as a hazard of the profession
• Routes of entry of viruses through the Urogenital System

  Small tears or abrasions in the penile mucosa and the epithelial lining of the vagina may permit the entry of virus, taken advantage of by Bovine herpesvirus 1, equine herpesvirus 3, and porcine papillomavirus
• Routes of entry of viruses through the Eyes

  Entry through the conjunctiva, with some adenoviruses and enteroviruses gaining entry this way
• Virus Tropism

  The capacity of a virus to selectively infect cells in particular organs
• Host Specificity

  Viruses may replicate only at or near the body surface through which they entered, or may enter the lymph or blood flow to reach their target organs
• Viral Spread - Local Spread


  Many viruses replicate in epithelial cells at the site of entry and produce a localized or spreading infection in the epithelium, with local sub-epithelial and lymphatic spread
• Viral Spread - Sub-epithelial Spread

  Virions that enter lymphatics are carried to local lymph nodes, exposed to macrophages, and may be engulfed for immune response development
• Viral Spread - Sub-epithelial Spread

  Some viruses can replicate in lymphocytes, which circulate through the blood and lymphatics, an effective means of disseminating viruses throughout the body
• Viral Spread - Viremia


  The blood is the most effective and rapid vehicle for the spread of virus through the body, with primary viremia and secondary viremia leading to infection in other parts of the body
• Interaction with the Macrophages

  Viruses multiply in macrophages, passing through capillaries and sinusoidal walls, using macrophages as a 'fake ally' in the 'Trojan Horse' mechanism of infection, utilized by Lentiviruses
• Mechanism of Infection - Infection at the Respiratory Tract


  Effects include local cessation of cilial beating, local loss of mucus lining integrity, destruction of epithelial cells, and in severe infections, acidosis, edema, and massive epithelial slough
• Mechanism of Infection

  1. Infection at the Respiratory Tract

  2. Infection at the Gastrointestinal Tract

  3. Infection at the Skin

  4. Infection at the Central Nervous System

  5. Infection of the Fetus

  6. Shedding from the Respiratory Tract

  7. Shedding from the Gastrointestinal Tract

  8. Shedding from the Skin

  9. Shedding from the Urinary Tract

  10. Shedding from the Genital Tract

  11. Shedding from the Blood and Tissues

  12. Infection without Shedding

  13. "Lifestyle" strategies of viruses in host cells
• Infection at the Respiratory Tract


  • Local cessation of cilial beating
  • Local loss of mucus lining integrity
  • Destruction of epithelial cells
  • In severe infections: acidosis, edema, massive epithelial sloughing
• Infection at the Gastrointestinal Tract


  • Rapid destruction of epithelial cells
  • Replacement by immature, transitional cells that cannot carry out normal functions
  • Leads to viral diarrhea
• Infection at the Skin

  • Erythema on exposed, hairless, nonpigmented areas
  • Infection may result in a rash
  • Individual lesions in generalized rashes: macules, papules, vesicles, pustules
• Infection at the Central Nervous System

  • Nervous signs: Change in behavior, Incoordination, Stumbling, Seizures, Coma, Death
• Infection of the Fetus

  • Most viral infections of the dam have no harmful effect on the fetus
  • Some blood-borne viruses cross the placenta causing severe cytolytic infections leading to fetal death, resorption, or abortion
  • Examples: Herpes-, Retro-, Reo-, Parvo- viruses