Pathogenesis of viral disease

sites of virus entry in a human

• eyes
• mouth
• nose
• scratch/injury
• needle stick
• resp track
• urogenital tract
• anus

transmission of communicable disease

direct

• horizontal contact - kissing/sex
• airborne droplets
• vertical contact (mother -> baby)
• vector

indirect (vehicles)

• touching objects/surface (contact) - fomites
• food, water, biological products
• airborne
  • droplet nuclei
  • aerosols

human to human

• blood transfusion/injection
• respiratory
• saliva
• fecal-oral
• venereal

zoonoses

infection acquired from animals

• biting arthropod vector
• vertebrate reservoir
• vertebrate reservoir/arthropod vector

body defenses

eyes

• tears
• lysozyme

resp. tract

• mucus
• ciliated epithelium
• aveolar macrophages

genitourinary tract

• washing of urine
• acidity of urine
• vaginal lactic acid
• lysozyme

skin

• anatomic barrier
• antimicrobial secretions

digestive tract

• stomach acidity
• normal flora

reaction of host cell to viral infection

• most viruses -> host cell death
• poxvirus, polyomavirus, papillomavirus -> proliferation of host cells
• RSV, measles, sendai, herpes -> fusion of membrane of adjacent cells to form multinucleate hybrid cells
• polyomaviruses, herpes, adeno, RNA oncogenic virus -> transformation of normal cells into malignant cancer cells
• rubella, some adenoviruses -> no histologic change in host cell appearance for several weeks

viral inclusion bodies in some human diseases

herpes

• nucleus

cytomegalovirus

• nucleus

rabies

• cytoplasm

adenovirus

• nucleus

measles

• nucleus

vaccina

• cytoplasm

determinants of viral disease

nature of disease

• target tissue
  • portal entry of virus
  • access of virus to target tissue
  • tissue tropism of virus (viral attachment protein)
  • permissiveness of cells for virus replication
• viral pathogen (strain)

immune status

• competence of the immune system
• prior immunity to the virus

severity of disease

• cytopathic ability of virus
• immunopathology
• virus inoculum size
• length of time before resolution of infection
• general health of the individual
• genetic makeup of individual
• age

types of infection

inapparent infections

• virus infect but doesnt cause anything (dont know ur infected)

acute infections

• see things that happen to infection
• localized
  • stay same place
  • virus go into person + replicate localized + localized spread -> disease + shedding of virus
• generalized
  • travel through bloodstream
  • virus -> entry -> blood/lymph so travel?
  • cause disease at target organs
  • shed
  • no significant effect on other organs
  • can spread thru nerves (ex: rabies)
    • Port of entry, implant, locally spread -> peripheral nerves instead of blood -> spread to target organ (central nervous system) -> can cause the disease and/or shed to go into the environment to spread
• congenital

persistent infections

• usually dont cause disease. Sometimes blow up

transformation

Pathogenesis of congenital viral infection

Can be congenital transmitted

Mother w/ fetus gets infected, then go to blood stream -> placental invasion -> fetus infected

- then baby may die in uterus, or recovers

- in some cases, baby born w/ disease

-> can lead to clinical infection which can lead to persistant infection, recover, or gets killed

-> can also lead to development of defects/abnormalities

Slow Infectious Diseases

bc of prions

How theyre diff from viruses

- viruses are filterable, so are prions

- ONLY have protein

- no morphology

- none of this kills prions

- not affected by proteases, heat, etc.

Immune system important against viruses

Prions have LONG incubation period – don’t know you have it for months/years

Prions are transmissible spongiform encephaloptathies

Deposits of extracellular proteins form plaques

transmittable

no signs of inflammation

transmission of disease to experimental animal by intracranial injection of a homogenate of diseased tissue and subsequent serial passage to further animals

scrapie - infectious disease of sheep known since early 1700s

2-3 year incubation period

cause irritability, itchiness and lack of coordination - fatal

transmitted to goats in 1957 and mice in 1961 for animal experimental studies

kuru: fore tribe of papua-new guinea

• "laughing death"
• restricted to that area
• loss of coordination (ataxia), partial paralysis, death
• devastated tribes for decades
• high familial prevalence in closely intermarried community
• affected children and women most

Ppl. In tribe being infected + dying for years

- usually women/children died

- what happened: scientist in autralia working for NIH

- he stopped in papua new guinea, heard abt this, became interested and started studying it

- the ppl who were infected suffered loss of coordination, partial paralysis, and death

"infectious" nature of kuru: TSE that resembles others

• noted it was similar to CJD, though diff parts of the brain
• noted it was similar to scrapie in sheep

CJD

• rare neurogenerative disease "spongiform encephlopathy"
• worldwide occurrence
• 10-15% inheritied (familial (f)CJD)
• shown to be infectious
  • also procedures: corneal transplant, intracerebral electrodes, injection of human growth hormone, or gonadotropin, tissue implants in brain

prion protein

Usually harmless and most ppl have the normal protein that can transform into the disease one (on top)

Becomes all twisted and becomes like bottom one (becomes infectious)

how this occurs

Normal one = PrPsc (protein of scrapie, normal)

PrPc – cellular form

If one of them changes, then cascade of proteins contacting each other and transforming them

-> hypothesize that it interacts and changes the protein

- so its not created, but modifies existing proteins

PrPC

form polymers as PrPC is converted

Aggregate – they form polymer -> causes disease

Progression of transmissible Creutzfeldt-Jakob disease

Progression of disease is slow

- infection occurs, and incubation can be 1-30 years

3-5 months before disease, see progrone

- get like dementia stage – see fibers are in brain -> leads to death

prion transmission

How spread

- some species transmission maybe be possible (scrapie from sheep, caused mad cow disease) btw species

- but no proof of showing can go to humans

Can amplify and cause more disease in a species

brain areas affected

• cerebral cortex
  • CJD eats holes in brain -> lead to dementia + death
• cerebellum
  • kuru + gerstman disease -> dementia
• thalamus
  • fatal familial insomnia
• brain stem
  • bovine spongiforn encephalopathy (mad cow disease) -> has infected thousands of cows

protein concentration in human vs animal brain

Study of brain extracts showed that there are 3 types of CJD where more concentrated protein in middle (humans)

But in animal, the top part is more concentrated

But type 4 in human is like the animal one

Pattern of prion masses:

Know diff types of infections (latent, acute, etc.)