13. Poxvirus Flashcards
are poxviruses enveloped or naked?
enveloped
what shape is the virus?
brick
is poxvirus small or large?
very big –> 200x250x300nm
3 characteristics of poxvirus genome
- dsDNA
- 130-300kb
- linear
what are the 2 main subfamilies of poxvirus?
- Chordopoxvirinae
- Entomopoxvirinae
what are the 2 main genera of Chordopoxvirinae that we will look at in this lecture?
- Orthopoxviruses
- Molluscipoxviruses
what type of diseases do poxviruses cause?
skin diseases –> can become systemic in organs
when was poxvirus eradicated?
1980
describe the clinical progression of smallpox (4 steps)
- infection by aerosol droplet
- virus incubates for some days
- leads to fever and rash all over body
- 30% ppl will die
what did Edward Jenner do?
- noticed that milkmaids never got smallpox bc exposed to cowpox
- took pus from cowpox lesions and gave to a young boy
- a month later, gave him pus from smallpox lesions and he never got the disease
what is variolazation?
give person the pus of smallpox –> develop smallpox but only have 1% chance of dying
what is vaccinia?
the strain of poxvirus in the vaccine –> but its not cowpox as Jenner originally used, we don’t know where it came from
describe the smallpox vaccine
- very stable so dried down in vial, then reconstituted upon use
- use bifurcated needle with a little bit of virus
- lesion will develop but goes away and patient is immune
what was the problem with the vaccinia in smallpox vaccine?
it was a live, replicating virus so in some cases it can spread and kill ppl –> esp if immunocompromised
is smallpox or monkeypox more pathogenic?
smallpox
where is monkeypox most common in the world?
Africa
how do you protect against monkeypox?
smallpox vaccine works for monkeypox
what are the 2 types of the virus? which is worse?
- West African
- Congo Basin –> more pathogenic and fatal
how is Monkeypox spread?
zoonotic infection from rodents
describe the imvamune vaccine
passaged thru chicken eggs so it can’t replicate in human cells –> much safer
this one is actually injected
which virus causes molluscipoxvirus?
molluscum contagiosum
is molluscum contagiosum common?
yes –> accounts for 1% of all diagnosed skin conditions
how does molluscum contagiosum spread?
by physical contact, mainly in moist areas, back of legs
is molluscum contagiosum severe?
no, it is self-resolving and doesn’t get systemic
where in the cell do ALL poxviruses replicate?
in cytoplasm –> nucleus remains intact
what is the shape of the core of the virus?
barbell
what contributes to most of the weight of the virus?
proteins!! holds many proteins inside
what are 4 special features of the poxvirus genome?
- terminal loops
- tandem repeats
- DNA is A-T rich
- has many bulges of 1 base that doesn’t match
describe the terminal loops
the ends of the DNA are covalently closed so there are no 5’/3’ ends
what are tandem repeats?
repeats of the same sequence on the end of the DNA
why does the DNA have a loose double-strand?
A-T rich (weaker) and mismatched bases
how are early/intermediate/late genes dispersed throughout the genome?
random locations within genome –> expressed based on promoters
what is the first step of poxvirus lifecycle?
attachment
how does vaccinia attach to its target cell?
vaccinia can infect any cell, not very specific –> likely by glycosaminoglycans
what is packaged in the virus?
ALL enzymes and factors required for early gene expression
why does the virus package all enzymes and factors required for early gene expression?
because poxvirus only replicates in cytoplasm, doesn’t go into cell nucleus
describe the genetic cascade (4 steps)
- all enzymes/factors for early gene expression packed in virus
- early mRNAs encode enzymes for viral DNA synthesis and factors for expression of intermediate genes
- intermediate mRNAs encode enzymes for expression of late genes
- late transcription factors activate the enzymes and factors for early gene expression to be packaged into new virus particles
how does genome replication begin?
early enzyme makes a nick in the terminal loop to allow exposed 3’ OH to be accessible by polymerase
describe the “self” priming mechanism of poxvirus DNA replication
uses its terminal repeats to replicate
what is resolvase?
encoded by virus to snip the end of the 2 completed genomes at the terminal loop once replication is complete
describe the steps of virus exit
- crescent-shaped lipid membrane
- Immature Virion forms full circle
- machinery brings in genome to form Nucleoid
- forms Mature Virion
- buds off golgi to get a 2nd membrane and form Wrapped Virion
- fully mature virus is released
in addition to intermediate stage enzymes and factors, what do the early genes produce?
secretes factors called VIROCEPTORS to attenuate the immune system
how do viroceptors attenuate the immune system
act as homologues of cytokine receptors or bind different immune factors to block their function
