Orthomyxoviruses Part 2

  1. Virion of ortho?
    they have a lot of proteins

    M2 ion channels are in short supply 

    Surface is dominated by HA and NA
  2. 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
  3. Distinctive Characteristics

    __ 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
  4. 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
  5. Entry and fusion of ortho?
    Fusion peptides snap up and grab our membranes, then bend back on themsef to bend the membrane
  6. ___ grab a hold of them and __.

    Other RNA viruses ahve simple life cycles in that they __. 

    With flu, there is a lot of __.
    host enzymes

    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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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

    lipid rafts

    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
  14. 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
  15. NA protein bypasses this how?
    it cleaves off sialic acid and then lets it float away
  16. 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.
  17. How many types of HA and NA are there?
    16 and 9
  18. 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
  19. 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
  20. 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
  21. Transmission of bird flu
    harder to spread due to the infection being deep and hard to cought up
  22. How are new viruse screated?
    antigenic drift and shift
  23. antigenic drift
    • 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
  24. Antigenic shift
    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
  25. 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
  26. Protection against the flu. What are the three weapons?
    • surveillance
    • vaccines
    • drugs
  27. Surveillance
    they monitor how many get the flu yearly and which ones, where it is widespread or lcoal and the temperature
  28. vaccines
    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
  29. The inactivated virus is sophisticated. Explain it.
    • - okay
    • - efficacy varies: 70-80% effective
    • - can be subject to errors
  30. FluMist
    • live attenuated
    • trivalent--made with three strains

    take hte HA and NA we are worried about. Put in attenuated onor virus--> new live vaccine
  31. How does fluMist act like rhinovirus?
    temp sensitive. 

    can't replicate at 37 but has to 34
  32. What are problems with FLuMist?
    can't be given to immunocompromised people

    ages 2-49 can get it
  33. Drugs
    drugs available on last strands
Card Set
Orthomyxoviruses Part 2
Test Two