MIDTERM 2/4

Viral infection does not equal disease. = NOT SYNONYMOUS
Some are subclinical infections (also known as asymptomatic or inapparent).
Virulence: Quantitative measure of a virus’s pathogenicity (can be pathogenic or non-pathogenic).
- Expressed in relative terms (e.g., "more virulent than...").
To cause disease viruses must:
- Infect their host.
- Spread within the host.
- Cause damage to target tissues.

For viruses to propagate:
- They must be shed in secretions/excretions into the environment.
- Taken up by another host or vector.
- Passed congenitally from mother to offspring.

Viruses exhibit significant differences in virulence.
Variation exists in infection outcomes among individual animals.
Viral virulence determinants are often multigenic.
Determinants of host resistance/susceptibility are multifactorial (host and environmental factors).

Application of molecular technologies has enhanced understanding of virulence and resistance determinants:
- Whole-genomic sequencing and the mapping of genetic factors.
Virus Strain Differences:
- Quantitative and qualitative differences affect:
  - Rate/yield of viral replication.
  - Lethal dose (LD).
  - Infectious dose (ID).
  - Organ/tissue tropism.
  - Extent of host cell damage.
  - Mode and efficacy of viral spread.
  - Disease characteristics induced.

Comparative analysis requires equal factors:
- Infecting dose of the virus, host age, sex, condition, and immune status.
Conducted using inbred animals but generalizations require caution.
Assessment methods:
- Disease causation, death rate, specific clinical sign identification, lesions.
- LD50: Dose causing death in 50% of subjects.
- ID50: Dose causing infection in 50% of subjects.
- E.g., Ectromelia virus strain data:
- BALB/c mice: ID50: 2 virions; LD50: 5 virions.
- C57BL/6 mice: ID50: 2 virions; LD50: 1 million virions.

Additional assessments include:
- Severity of infection.
- Location and distribution of histological/ultrastructural lesions.

Progress in molecular biology aids in identifying genetic factors tied to virulence.
Genetic sequencing elucidates potential virulence determinants.

Viral infections are generally less pathogenic in natural hosts than in exotic/introduced species.
- Example: Myxoma virus causes benign fibroma in natural hosts but fatal infection in European rabbits.
Some zoonoses are severe in humans but mild in reservoirs.

Expression of receptors on target cells is crucial for host resistance/susceptibility.
More conserved receptors correlate with a wider host range.
- E.g., Rabies virus uses sialylated gangliosides and acetylcholine receptors; infection is often restricted to myocytes, neurons, and salivary gland cells.

Changes in viral attachment can lead to the emergence of variant viruses with altered tropism.
- Example: Porcine respiratory coronaviruses evolved from transmissible gastroenteritis virus due to significant deletions in spike protein coding.

Via respiratory tract, gastrointestinal tract, skin, and other routes (e.g., genital tract, conjunctiva).

Mucociliary blanket protects respiratory tract:
- Mucus traps inhaled virions, and cilia moves them upward for expulsion.
- Larger particles trapped in nasal cavity; smaller particles reach alveoli.

Viruses can enter via contaminated food/drink.
Defenses include stomach acidity, mucus, antimicrobial enzymes, bile, and immune mechanisms.
Enteric pathogens primarily infect GI epithelial cells and M cells in Peyer’s patches and are often acid-bile resistant.

Conjunctival entry through tears, and genital route transmission via small abrasions during sexual activity.

Initial exposure via aerosol, then replication in lymphoid tissues, leading to primary and secondary viremia extensions across various organ systems.
Clinical signs appear at peak viral shedding; potential lethality follows from immune suppression and secondary infections.

Vacuolation, ballooning degeneration, syncytium formation, and different forms of inclusion bodies.