Virology III - Infection & Disease Flashcards
virulence
ability of a virus to cause disease (pathogenicity)
why do viruses cause disease
to optimize survival
- want the clinically sick animal to shed the virus
can also be an accidental by product of infection
what are the factors that determine virulence
host
virus
environment
what virus factors determine virulence
- genome sequence
- epigenetic factors
what host factors determine virulence
- genome sequence
- epigenetic factors
- adaptive & innate response
- receptor distribution
what does receptor distribution determine
viral tropism for specific hosts/sites/tissues
what is the iceberg of disease severity
assessment of most common virulence outcomes
- exposure w/o infection
- subclinical infection
- mild disease
- moderate disease
- severe disease
- death
what are the steps of host infection
- entry and replication into initial host cell types
- local or generalized spread in host
- shedding from host
- clearance from host
what are the routes of entry into a host
- respiratory
- alimentary
- conjunctiva
- skin
- systemic (capillary)
- scratch/bite
- urogenital tract
what is required by the virus in order to spread locally or systemically
must evade host immune system and inflammatory responses/barriers
what is important for adequate shedding of the virus
virus must reach the correct site for shedding at a concentration high enough to ensure infection of the next host
what mediates clearance of a virus
adaptive immune response
may not be complete - can get intermittent shedding of chronic infections
local infections
route of virus entry = route of shedding
ex. respiratory pathogen that gets shed via the respiratory tract
systemic infections
route of virus entry = one route of shedding, but shedding also occurs at an additional site
ex. respiratory pathogen that gets shed via the respiratory and urogenital tract
what are the steps of viral spread
- virus crosses epithelium
- primary replication occurs inside macrophages OR free in blood
- travels to LN
- secondary replication occurs in LN
- virus travels in blood either cell-free or cell-associated
- causes viremia
why might a virus target dead end sites (ex. brain)
dead end sites = locations in the body where the virus is not able to shed
goal is to alter behavior to make shedding more likely
ex. rabies - shed in saliva but travels to the brain in order to increase biting behavior –> increases transmission in saliva
what are the 5 mechanisms of invading the CNS
- neuromuscular junctions
- sensory neurons
- neurons in nasal epithelium
- leukocytes that enter BBB
- endothelium
steps and example of NMJ invasion
- bite wound injects virus into muscle
- replicates in muscle cells
- crosses NMJ
- travels up motor neuron
- replicates in CNS cells
- infects salivary glands
ex. rabies - site of bite wound determines time required to show clinical signs
steps and example of endothelial invasion
- virus in blood (viremia) infects endothelium
- crosses BBB
- replicates in CNS cells in brain and spinal cord
ex. WNV; may also use “Trojan horse” mechanism of hijacking WBCs
what are the 4 ways that viruses can cause injury/disease
- cell injury (cytocidal)
- persistent, productive
- persistent, non-productive
- transformation
cell injury/cytocidal
- has cytopathic effects
- causes inhibition of host protein, RNA, and DNA synthesis –> apoptosis
- HAS production of infectious virus
cytopathic effects: lysis, apoptosis, necrosis, syncytia, cytoskeletal disruption, etc
persistent, productive
- NO cytopathic effects
- tries to “hide” from the host cell
- some loss of cell division/metabolic disturbance
- HAS production of infectious virus
persistent, non-productive
- no loss of host cell functions
- does NOT result in production of infectious virus
resumption of productive infection may be triggered by trauma
transformation
- alters cell morphology to produce tumors
oncogenic DNA virus: do NOT produce infectious virus
oncogenic retroviruses: DO produce infectious virus
mechanism of GI injury
- infection of GI enterocytes
- lysis of enterocytes –> reduced absorptive surface –> diarrhea
- diarrhea causes loss of fluid and electrolytes
- causes clinical signs
clinical signs of viral GI injury
dehydration, hemoconcentration, acidosis, hypoglycemia, electrolyte imbalances
mechanisms of CNS injury
- systemic or nerve cell infection
- virus crosses BBB or BCSFB via neuroinvasion mechanisms
- infects neurons and glial cells
- causes inflammatory cell influx
- inflammation –> meningitis, encephalitis, myelitis
- causes clinical signs (neurologic dysfunction)
what are persistent viral infections
viral shedding can begin before, during, or after clinical signs appear
infectiousness increases and decreases with intermittent viral shedding
