Smallpox Flashcards
Detection of poxvirus
Found in cytoplasm
Both budding and lysis
Histologic staining -> see “inclusion bodies”
Autoradiography with 3H-thymidine -> “foci”
Structure of poxvirus
Large ds DNA genome
Has own DNA-dep RNA polymerase (vs all other DNA viruses use cell)
Contains lipid but made in cytoplasm
Large, assymetrical bricks
Two forms! Requires two antibody responses
Enveloped - via budding
Unenveloped - via lysis - stable in env’t
Molluscum contagiosum
Only poxvirus we should ever see
Intimate skin-skin contact -> 2-8 weeks -> white papules
Self limiting but long time
Grows poorly in culture
Immune compromise -> widespread severe infections
No specific treatment
Poxvirus replication
dsDNA genome + DNA-dep RNA polymerase
-> cytoplasm -> transcription -> mRNA
-> virions, other enzymes (ex DNA poly) ->
assemble in cytoplasm
RNA polymerase allows it to replicate in cytoplasm
All other DNA viruses must be in nucleus to transcribe mRNA
Smallpox pathogenesis
Aerosol -> resp -> multiplies in mucosa, lymph (mild URI) ->
First viremia -> lungs, liver, spleen ->
Second viremia -> pantropic including skin ->
Papules, vesicles, pustules
Similar damage to internal organs -> 20-80% mortality!
Smallpox transmission
Not infectious until pustules appear
Lesions in oral mucosa -> aerosol -> respiratory
Pustules - also contain infectious virions
- unenveloped/stable -> innoculation, giving blankets to Native Americans, transport in cotton from India…
Smallpox innoculation
Variolation = transfer infectious virion via abnormal route
- pustule -> scratch on arm -> less severe infection + immunity
- first used in China -> 18th century West
Vaccination = transfer of infectious cowpox virus -> immunity from smallpox
- Jenner, milkmaids….
- vaccinia virus = live, not exactly cowpox (has been mutated)
Smallpox eradication
Only successful eradication of human disease
All via live vaccinia vaccine
Mass immunization in many areas of the world
Case identification -> ring vaccination of exposed populations in Africa, SE Asia
Possible due to:
Vaccination is effective up to 4 days post-exposure
Every case is symptomatic (can identify)
No human reservoirs
Single serotype
Politics (fear of spread into Europe, paternalism…)
Money (cheap stable vaccine, doesn’t need hollow core needles)
Vaccinia complications
Live vaccinia virus!
Post-vaccinia encephalitis
Vaccinia necrosis (cellular immunity defect)
Eczema vaccinatum (spread dt pre-existing eczema)
Generalized vaccinia
Myocarditis/pericarditis
Can be treated with pooled IgG (passive immunization)
Rabies structure
Rhabdovirus Bullet shaped Enveloped Helical nucleocapsid Single (-) RNA - carries RNA-dep RNA polymerase
Rabies pathogenesis
Bite with infectious saliva ->
Trophic for nerve cells (does not require viremia) ->
Travels via nerves -> CNS -> salivary glands
Long incubation (weeks to months) Almost always fatal (success with induced coma?)
Neural pathway
Virus is within neurons
Herpes
Rhabdo (rabies)
Does not require viremia
Vs other viruses cause viremia -> encephalitis or meningitis
Presentation of rabies
Nonspecific (fever, anorexia) Hydrophobia! Fear of water dt extreme pharyngeal pain - humans don't get "mad-dog" aggression Paralysis Coma Death
Speed of symptoms from location (ie bite to the head vs arm/leg)
Diagnosis of rabies
Cytoplasmia Negri inclusions
(use fluorescent Ab)
vs Herpes -> nuclear inclusions
Rabies vaccination
Effective after bite but before clinical symptoms (passive + active)
- passive immunization (hyperimmune IgG) +
- killed vaccine - 5 doses over multiple months
- grown in diploid cells -> killed with chemicals
(safe, does not give you allergic encephalitis)
Prophylactic - killed vaccine for vets, travellers, etc
