Lecture 10 Flashcards
(29 cards)
What is the social/historic importance of poxviruses?
- 1st virus to be eradicated
- 1980 WHO declared smallpox free Earth (greatest achievement of modern medicine)
- Conquistador brought small pox to America and ravaged populations who had never been exposed to such a virus, good for colonialism
What’s the importance of small pox in 20th century death?
- grandaddy of poxviruses and viruses in general
- ravaging humanity for thousands of years (mummies have it too)
- 60s still infecting 10s of millions and 1-2 million in horrific way
- 400 million deaths in the century
Family of poxviruses
Poxviridae
Subfamily of poxviruses
Chordopoxvirinae
Morphology of poxviruses
- enveloped
- brick shaped
- 200-250x250x300 nm
- Genome: dsDNA 130-300kb (lots of functionality in there) / linear
What subfamily of poxviruses only infect insects?
Entomopoxvirinae
What is the subfamily that interests us?
Give important genera and species per genera
Chordopoxvirinae
- Orthopoxviruses: camelpox, cowpox, smallpox, monkeypox, racoon pox, skunk pox, vaccinia, variola(small pox)
- Molluscipoxvirus: molluscum contagiosum
Fun fact: almost every animal has its own poxvirus associated to it
Diseases caused by each of the important species?
Almost always condition of the skin (lesions)
- Variola (only natural host is humans), small pox, systemic, general rash, extinct except in labs as frozen stocks in CDC level 4 biohazard and Russians, bioterrorism threat
- Monkeypox: nothing to do with monkeys, rodents are natural reservoir (pass to humans, zoonosis), systemic, general rash, rare zoonosis
- Vaccinia: gift from god, smallpox vaccine (not actually cowpox as originally thought, not even mutation from cowpox, god knows what the natural reservoir), local skin lesion
- cowpox: famous cause infection of cows, important in eradicating small pox, local skin lesion, rare zoonosis
- Molluscum contgiosum: multiple skin lesions, human transmission
Statistics about smallpox in comparison to monkey pox:
Monkey pox: fairly low mortality rate, 60k cases worldwide, less than 30 deaths, small pox is way more contagious and lethal
Small pox: monkey pox on steroids, lifelong immunity if you survive though, 10-30% mortality rate, India67 strain 80% mortality rate
COVID-19: 0.1-0.2% mortality rate
Clinical progression of small pox
Infection through droplet/aerosol/skin-skin contact pustules, bedding all that jazz
Incubation: 7-17 days
Fever: 3-4 days
Enanthem: 2 days rash on mucous membranes mouth and down throat feels on fire when swallow
Exanthem: 12-32 days rash all over body extremely painful, extent of rash depends on severity
Symptoms small pox: fever 3 days before rash, appearance all over body, palms and soles slow, death os centrifugal
usually 10-30%
- skin virus (can still survive) but can go systemic (no treatment, accept death), infecting endothelial cells, Dif tissues, lead to organ and tissue failure and eventually death
Chicken pox: actually herpesvirus lmao
Clinical diagnosis: macule, papule, vesicle, pustule, crusted scab
The Edward Jenner story
SOOOOO yeah the parents of this kid asked Jenner to barioliez him (1000 years prior, people would take smallpox directly into the skin, usually stays localized and chance of dying was only 1% vs 10-30% so yeah), but my man heard about the cow maids, took cowpox puss and incision in one arm, rash that went away, 1 month later incision in other arm smalll pox => kid was protected (localized lesions that went away, immunity to small pox)
Mans discovered vaccination even before germ theory of disease, had no clue what viruses were, so yeah he’s a dope man
Small pox dryvax vaccine
Can be lyophilized, dried out and stored and shipped, very stable and then when actually used only need smaller little amount that is administered with a bifurcated needle, develops rash that scabs and then falls off
Live replicating virus so like 1/1000 had very severe complications and about 1/1 000 000 did die (could become systemic of patient was immunocompromised)
Still used in US army
How was small pox eradicated?
- well virus can’t hide in other reservoirs like coronaviruses bats and other zoonotic viruses (only infects humans)
- No hiding of cases, easy to find since there was no such thing as asymptomatic patients
- The very existence of vaccinia which literally fell from the sky (okay not literally, but you get the point)
Monkeypox epidemiology
- Mostly confined to Africa, although outbreak in US from rodent reservoir (about 100 cases in 2003)
- Small pox vaccine protects (also an orthopoxvirus though not quite as infectious nor contagious, does not spread as well)
- 2 clades of the virus Dif sequence:
- West African (mild version, one in the world)
- Congo basin (tends to go all over the body, can be systemic) as high as 10% mortality rate but then again access to medical care in Africa is not great
- Seems to peak in the world right now, mostly gay men get it although not considered an STD but I mean yeah skin-to-skin contact (fluke of nature) came from west Africa, went to Spain got massages, was gay with other men and the rest was history
What is the newer version of the small pox vaccine today?
IMVAMUNE: still vaccinia but passed through chicken embryo fibroblast 100s of times => really adapted to replicate in chicken cells => now barely replicates in mammalian cells
Is safer but less effective, need more of it, because doesn’t cause as big of an infection as dryvax (live virus)
Even works fairly early on in monkey pox infection (when rash hasn’t set in yet)
Molluscum contagiosum fun facts
- Rash localized in legs, in extremities, self-resolving after a few weeks, not so dangerous but is quite prevalent, vaccine doesn’t help as it’s not an orthopoxvirus
- In the US, accounts for 1% of all diagnosed skin conditions
- Spreads by physical contact (skin to skin, popular in college dorms)
Where do poxviruses replicate?
- Cytoplasm unlike most DNA viruses (in nucleus)
- Doesn’t even need uncle, replicated in enucleated cells
- In cytoplasm forms vacuoles, virus replicating factories
How do we know what we know about poxviruses?
- Study cell biology with vaccinia (safe)
- outlawed to work with small pox, last person to die from it was a lab worker
What is the core of poxvirus?
In brick, there is peanut, peanut has DNA
What is the purpose of lateral bodies ion poxvirus?
- Holds all proteins (like 75 proteins) needed for replication (RNA pol, TFs, etc.) since replication in cytoplasm, no nucleus
Some cute stuff about poxvirus structure?
2 envelopes/ 90%. made up of protein / Dif proteins on the membrane for Dif things enter actress viral entry
Particularities about the poxvirus genome?
The 5’3’ ends are fused and closed as a terminal loop, just one big strand of DNA
- 200 kbp
- Tandem repeats, important for replication
- 2 ends are very AT rich and mismatches with little bases sticking out => ends are kinda open and mushy base pairing, not ver hybridized together
- All different ORFs, codes for about 200 different proteins all over the genome, different classes of proteins based on temporal regulation (expression dependent on time) regulated by specific TFs at specific promoters (early, intermediate, late and not expressed), no splicing like most DNA viruses because does not code for splicing factors
Poxvirus replication attachment and entry
virtually any mammalian cell because general mechanism of entry probably uses glycolipids/glycosaminolipids
Fusion of membrane with plasma membrane, entry of the core
Every thing is in with early enzymes like RNA pol and TFs
Early mRNA transcripts
Include DNA polymerase, intermediate TFs, RNA polymerase, growth factors immune defines molecules
