Virion of ortho?
they have a lot of proteins
M2 ion channels are in short supply
Surface is dominated by HA and NA
Life cycle of ortho...
Flu is an odd virus.
RNA virus that never uses DNA yet replicates in the nucleus
- 1) Binds to cells--> endocytosis
- 2) pH drop--> fusion in endosome
- 3) release of gene segments in nucleus
- 4) protein synthesis
- 5) virus buds
__ is made as one large protein.
In it's mature form, there are __. The __ helps it. There is a __.
- two parts that are held by S-S bonds
- cleavage sequence
- hydrophobic section of residues called the fusion peptie
Because HA is cleaved into two subunits....what?
the fusion peptide separates out and intermixes with the membrane, bringing the host and virus cell membranes close together
Entry and fusion of ortho?
Fusion peptides snap up and grab our membranes, then bend back on themsef to bend the membrane
___ grab a hold of them and __.
Other RNA viruses ahve simple life cycles in that they __.
With flu, there is a lot of __.
shuttle them into the nucleus
get into cell, get to ribosome, make proteins, assemble, bud, and exit
shuttling in and out that has to happen
Explain the entry of influenza RNA
has to get into the nucleus to become + RNA, which then gets transported to protein synthesis machinery
Afterwards, they go back into the nucleus if they are polymerases to synthesize the RNA
What is the mechanism for viral polymerase functionality?
Flu polymerase has the capacity to make poly-A tails, but does not have the capacity to make a cap for positive sense RNAs it makes
Explain the cap snatch procedure
- 1) cleavage of cap of cellular pre-mRNA that is in nucleus and should be exported; PB1 cleaves at A; PB2 binds to cap
- 2) The cap is used as primer to make viral mRNA
- 3) You transcribe a pre-capped mRNA
- 4) The final viral mRNA is ready to be exported and made into protein as it is already capped and has a poly-A tail
The first step of the Cap snatch is pretty non-specific. Any mRNA they can find, they __
They are __ that take whatever they can, using it to __
- take the cap of it
- obligate parasites
- turn their own genes into proteins
The second to last step of the Cap Snatch takes about the poly-A tail. Explain.
There is a poly-U tract that is shorter than the poly-A tail
The RNA pol stutters and loses its place a little bit and starts over again, leading to more A's in the mRNA--> longer poly-A tail
There is potential for splicing of these RNAs.
The unspliced RNA makes the matrix protein and NS1 that interferes with the immune response
Splicing creates M2, the ion channel, and NS2, which elps fight off the immune system
The envelope proteins are __.
They accumulate in __ and then __.
For a lot of viruses, that is all there is. For influenza, what is the last step?
made and exported through the cellular machinery, along with the M2 protein
bud with exactly one copy of the genome segment
NA is the opposite of HA. It is a molecule that helps the virus release itself from cells it is budding off of and allows infection to a new and budding cell
NA activity--why is it needed?
HA binds to sialic acid but there may be problems: when the virus buds, there's potential for it to bud out and reattach itself to more sialic acid residues on the same cell and go back in, rendering infection futile
NA protein bypasses this how?
it cleaves off sialic acid and then lets it float away
If you decrease NA activity in a virus particle, what happens?
NA has the important function of..
it gets into cells more readily but has a harder time getting out and vice versa
allowing the virus to be released by cells.
How many types of HA and NA are there?
16 and 9
Sialic acid types
there are alot of kinds in different places and in different species
HA may vary in their affinity for certain sialic acids over others
If we get seasonal flu, it __.
binds sialic acids that are concentrated high up on our respiratory tract
we can cough it out and sneeze it out
our body is less affected by losing these cells
With bird flu, what happens?
H5 molecules infect alpha 2,3 chains, whereas H1N1 affects 2,6 chains
When we have bird flu, the infection is deep in our lungs, causing 40% of people with it to die
Transmission of bird flu
harder to spread due to the infection being deep and hard to cought up
How are new viruse screated?
antigenic drift and shift
- slow accumulation of point mutations
- often in HA and NA molecules, proteins exposed to our antibody responses
may be due to RNA pols not having as high a fidelity as DNA polymerase, leading to mutations and different variants of the virus
This causes seasonal flu
occurs at regular intervals
entirely new gene segments from different types of flus to create a chimeric virus
you have a completely new type of protein that catches everyone off guard
This happens because of two distinct features of the virus. What are they?
happens in different gene segments, making it easier to swipe them out
they have the ability to affect many species
Protection against the flu. What are the three weapons?
they monitor how many get the flu yearly and which ones, where it is widespread or lcoal and the temperature
have to be designed every year
the flu shot is an educated guess: Which ones are most likely to hit America in the winter. In the spring, they look at activity on the other side of the planet and take note of new strains
They then produce vaccines in eggs using three strains. They then inactivate it, mix it with detergents to break apart the particles, and run through a centrifuge
The inactivated virus is sophisticated. Explain it.
- - okay
- - efficacy varies: 70-80% effective
- - can be subject to errors
- live attenuated
- trivalent--made with three strains
take hte HA and NA we are worried about. Put in attenuated onor virus--> new live vaccine
How does fluMist act like rhinovirus?
can't replicate at 37 but has to 34
What are problems with FLuMist?
can't be given to immunocompromised people
ages 2-49 can get it
drugs available on last strands