2_PathogenesisofViruses

Pathogenesis of Viral Infections and Diseases

Prepared by Khristine Kaith S. Lloren, DVM, MSc, PhD College of Veterinary Medicine and Agricultural Sciences De La Salle Araneta University

Viral Infection vs. Disease

• Viral Infection: Not synonymous with disease.

• Subclinical Infections: Some viral infections can be asymptomatic or inapparent.

• Virulence: Quantitative measure of the pathogenicity of a virus, indicated in relative terms (e.g., "more virulent than...").

• Requirements for Viruses to Cause Disease:

  • Infect their host.

  • Spread within the host.

  • Damage target tissues.

Virus Shed and Transmission

• Viruses must be shed into the environment through secretions or excretions.

• Routes of transmission include:

  • Taken up by another host or vector.

  • Passed congenitally from mother to offspring.

• Virus Propagation: Must be transmitted to another susceptible host.

Interaction of Viral Virulence and Host Factors

• Viral virulence varies greatly among different viruses.

• Outcomes of infections differ between individual animals.

• Variation within viruses of the same species is often due to multiple genes contributing to individual virulence.

• Determinants of Host Resistance/Susceptibility: Multifactorial, involving:

  • Host factors (genetics, immune response).

  • Environmental factors.

Molecular Technologies in Virulence Mapping

• Molecular technologies aid in identifying the genetic determinants of virulence in many viruses.

• Techniques used include whole-genomic sequencing.

• Virus Strain Differences: Determined by factors such as:

  • Rate and yield of virus replication.

  • Lethal dose (LD50): dose required to cause death in 50% of animals.

  • Infectious dose (ID50): dose that causes infection in 50% of individuals.

  • Organ-specific tropism and extent of host-cell damage.

Assessment of Viral Virulence

• Factors for comparison include:

  • Infecting dose of virus, age, sex, condition of host, immune status.

• Use of inbred animal assays (e.g., mice) is helpful but should be extrapolated carefully to other species.

• Virulence can be assessed through:

  • Ability to cause disease, death, specific clinical signs, or lesions.

  • Important metrics include LD50 and ID50 examples from ectromelia virus.

Host Resistance/Susceptibility Determinants

• Viral infections are typically less pathogenic in natural hosts versus exotic or introduced species.

• Example: Myxoma virus is benign in wild rabbits but pathogenic in European rabbits.

• Some zoonotic diseases are severe in humans but subclinical in animal reservoirs.

Receptor Expression and Virus Attachment

• The expression of critical receptors on the target cells is crucial for host resistance.

• More conserved receptors lead to a wider host range (e.g., Rabies virus).

• Changes in viral receptor binding can lead to variant viruses with altered tropism and disease potential.

Routes of Viral Entry

Via the Respiratory Tract

• Protected by mucociliary blanket.

• Inhalation leads to the trapping of virions in mucus, which are subsequently removed.

• Different particle sizes have specific entry paths into the lungs.

Via the Gastrointestinal Tract

• Entry through consumption of contaminated food/drink.

• Defense mechanisms include stomach acidity and digestive enzymes.

• Viruses typically affect epithelial cells in gastrointestinal mucosa.

Via the Skin

• Skin acts as a mechanical barrier; breaches can predispose to infections.

• Viral entry can occur through insect bites or medical procedures.

Via Other Routes

• Entry can occur through conjunctiva or via sexual transmission.

Mechanisms of Viral Spread

Local and Systemic Dissemination

• Local spread may result in shedding from the initial route of entry.

• Viremia allows for spread through lymph and the bloodstream, leading to infections in multiple organ systems.

Example: Canine Distemper Pathogenesis

• Initial viral replication occurs in lymphoid tissues, followed by primary viremia.

• Secondary viremia results in shedding from respiratory, urinary, and conjunctival mucosa.

• Clinical signs appear alongside peak viral shedding.

Viral Adsorption Mechanisms

• Successful virus adsorption relies on proper receptor sites on host cell surfaces.

• Example: Orthomyxoviruses utilize glycoproteins to bind to specific receptors for entry.

Pathological Changes in Infected Cells

• Cytopathic effects include:

  • Vacuolation, ballooning degeneration, syncytium formation, hyperplasia.

• Inclusion Bodies: Abnormal structures resulting from viral replication seen in host cells.

• E.g., Negri bodies are a characteristic of rabies infection.