Orthomyxoviruses Part 2

they have a lot of proteins

M2 ion channels are in short supply 

Surface is dominated by HA and NA

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

HA

• two parts that are held by S-S bonds
• cleavage sequence
• hydrophobic section of residues called the fusion peptie

the fusion peptide separates out and intermixes with the membrane, bringing the host and virus cell membranes close together

Fusion peptides snap up and grab our membranes, then bend back on themsef to bend the membrane

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

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

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

• 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

• take the cap of it 
• obligate parasites
• turn their own genes into proteins

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

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

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

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

it cleaves off sialic acid and then lets it float away

it gets into cells more readily but has a harder time getting out and vice versa

allowing the virus to be released by cells.

16 and 9

there are alot of kinds in different places and in different species

HA may vary in their affinity for certain sialic acids over others

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

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

harder to spread due to the infection being deep and hard to cought up

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

happens in different gene segments, making it easier to swipe them out

they have the ability to affect many species

• surveillance
• vaccines
• drugs

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

• - 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

temp sensitive. 

can't replicate at 37 but has to 34

can't be given to immunocompromised people

ages 2-49 can get it

drugs available on last strands