Poxviruses Flashcards
Genomes of poxoviridae family
Linear dsDNA (large)
- attached by A-T rich hairpins
Center region: structural proteins and essential enzymes
Ends: virulence factors, host-range, immunomodulators
Structure of poxoviridae family
- capsid (dumbell)? no exact shape for nucelocapsid
- enveloped or double enveloped based on time in life
What is the receptors for poxoviridae family
glycosaminoglycans
poxoviridae gene expression phases: (3)
Early phase: NS proteins necessary for replication
Intermediate phase: small class of genes for late transcription factors
Late phase: genes encoding structural proteins
(all takes 12 hours, then host dies (lytic) when virions release, or transfer to neighbouring cells)
Where do pox viruses replicate and how?
cytoplasmic replication
viral genome encodes their own DNA dependant RNA polymerase (DdRp)
then assembles also In cytoplasm and gets envelope from Golgi
pox virus entry and fusion
pox viruses need a few proteins for attachment (glycosaminoglycans such as Herman sulphate), and a lot for fusion (Entry fusion complex)
What are pox virus lateral bodies
release after fusion of virus, proteinaceous delivery packets that have immunomodulatory effects
with many viral protiens some of which inhibit interferon IFN system to protect virus from out response (H1 phosphorlyzes STAT 1)
where does transcription of EARLY viral mRNA take place
intact cores (nucleocapsid) were DpRp and VETF are (vaccinia early transcription factor)
what are the early proteins (100 genes, 1/2 the genome)?
1- promote intermediate phase
2- protiens required for replication and uncoded genomes (make replication factories by stealing ER membranes)
3-virokine protein synthesis (mimic human cytokines)
how does the replication happen in poxviruses by DNA pol
there is terminal repeat (loops) that act as primer to initiate DNA synthesis
what helps assembly of viral particles
1- Viral membrane assembly proteins (A6, A11, A30.5 H7 and L2)
2- scaffold structural proteins that viruses assemble on
3- steal membrane from Golgi
Parts of assembly of pox virion (2 parts)
1- immature virions (ER derived vesicle) core proteins go in and the DNA goes in and lateral bodies
2- mature virions (once envelope is taken by Golgi)
How do pox viruses get out of the cell
- mature virions (MV) trafficked along microtubules to glow
- MVs they get wrapped in double envelope ( an extra lipid envlope) becoming intracellular envloped virions IEVs
- transported to cell surface and released by exocytosis
- some make actin tails to propel away from cell (A36 protein)
Pox viruses are so good at immune evasion, how?
- retrotransposition: capture and adapt host genes
-solubale and cell surface TNF receptors (to trick immune system)
-soluable IL-1B- binding protien (inhibits warning sign) - soluble type I and II IFN binding proteins (inhibits innate immune response)
- chemokine binding proteins
- NF-kB inhibitors (TF that turn on inflammation)
-apoptosis inhibitors
-inflamasomes and paraptosis inhibitors
RNA viruses can mutate quickly but DNA ones can’t, so how they they evolve to overcome host defense
genomic accordion: VACV expand and retract the number of certain genes
(Also in giant viruses?)
Myxoma virus
rabbit specific pox virus
introduced by Australia to reduce the rabbit population brought from England. virus evolved and started killing more than rabbits
Mpox (formerly Monkeypox)
- first found in primates
- turns out monkeys are not the reservoir host (rodents)
- now outbreaking again due to decrease in smallpox vaccination
Two clades of mpox virus
clade I (10% fatality) clade II (less than 1%) fatality rate, why??
how does mpox transmit
close contact with infected humans/animals, body fluids, respiratory droplets, skin lesions, (2022 sexual transmission)
- local replication
-spread via lymphatic system and blood - prodrome phase (fever, headache, malaise)
-secondary spread via blood (viremia_
post-prodromal phase: skin lesions
Small pox (four clinical forms)
1 - ordinary small pox (85% of cases)
2 - modified-type small pox (in people who were vaccinated, milder)
3 - flat type smallpox (rare, rash stayed flat and people had very high blood pressure) suggested to be caused by a deficiency of T cells
4 -hemorrhagic smallpox: not protected by vaccination, people died after 5-6 days of symptoms
Variolation
collect scabs of someone who was sick, make it powered, and put it up someones nose (hoping it’ll be a mild infection)
why could we eradicate smallpox?
- no animal reservoir
- no asymptomatic or sub clinical infections
- effective vaccine
-way to show vaccination (scar) - intense surveillance and dedicated team (ring vaccination contacts and contacts of contacts)
