orthos (standard) myxo (mucous)

causes influenza.

A/B have 8 segments of (-) RNA , C has 7.

GENOME:

- segments called RNP (RNA + proteins)

-6 of the segments code for 1 protein while the other 2 code for 2 proteins

- each RNP is made up of 4 diff proteins (can have multiples of one type of protein) and RNA (one of the protein is nucleoprotein, which approx. binds to 20 nucleotides)

- each RNP is associated with 3 polymerase polypeptides (PB1, PB2 PA), which function together to make RDRP complex

STRUCTURE

- pleomorphic (80 - 120 diameter)

- enveloped, with spikes sticking out (gylcoproteins)

the GPLYCOPROTEINS:

hemagglutinin (HA) made up of 3 identical subunits (is the anti-receptor)

neuraminidase (NA) made up of 4 identical subunits (used to detach from hose cell after replication cycle)

- 5:1 ratio of HA to NA, and around 500 in total that cover the surface of virus

HOST RANGE

humans animals and birds, pigs and birds act as reservior for type A, which is associated with epidemics and pandemics

receptor: N-acetylneuraminic acid on mucoproteins. very common!

natural environment: upper respiratory tract

REPLICATION CYCLE

1. each individual receptor/anti-receptor has low affinity, but due to the multiple number of interactions, there’s high avidity. HA is cleaved by this extracellular protease secreted by host. now HA is HA1 and HA2. clathrin coated pits form, and virus is taken up by phagocytosis,

2. the cathrin coat is removed, and vesicle fuses with endosome (low in pH), which triggers change in HA that results in the receptor binding region to be shifted back and the FUSION peptide is shifted forward, and inserted into endosome. and the envelope and endosome membrane FUSE. the fusion peptide is on HA2. contents go into cytoplasm

3. RNPs enter nuclear pore, which involves the NP proteins (doesnt involve cell structures)

4. the - strand RNA is coped by the RDRP complex into mRNA, which is capped with cell mRNA components (CAP STEALING)

5./6. mRNA goes into cytoplasm and gets translated. some of the mRNAs need to be spliced, because recall that 2 of the -strand RNA codes for 2 proteins.

7./8./9. mRNAs that specify viral envelope proteins are translated by ER ribosomes

10./11./12. newly made viral proteins that need to be packaged are transported back to nucleus where they catalyze the synthesis of progeny genome. +strand is made and then -ve strand is made. they are made in the form of NEUCLEOCAPSIDS

13./14. M1, which is a matrix protein, binds to the - RNA and causes synthesis of mRNA to stop, and export of progeny genome with proteins are released to cytoplasm

15./16. HA and NA are transported to cell surface and go into the cell membrane

17./18. the nucleocapsids associate with M1 proteins and the NS2 proteins are transported to cell membrane and associated with regions containing HA and NA

19. virus bud off. no cell membrane proteins are found of envelope. NA removes the sialic acid from surface of infected cells

DETAILS OF mRNA SYNTHESIS

RDRP complex binds to 5’ of - RNA, and a cell mRNA is bound to the 5’ end, and all is cleaved off except for the 5’ cap ( and 13 nucleotides)

+ 5’ CAP———>direction of RDRP

- 3’—————————————-5’

this creates an incomplete + strand, cuz theres a pandhandle structure formed at the very end of synthesis, ( at the - 5’ end). this panhandle is important in termination of transcription.

SYNTHESIS OF COMPLETE + STRAND, and consequently the progeny genome

no cap stealing is involved

production of full sized is regulated by the amount of FREE NP proteins present in the cell (increase in NP mean production of full sized strand)

and it can now make + RNA without primer

PATHOGENICITY OF INFLUENZA

antigenic drift: minor changes in HA and/or NA due to changes in the AA sequence. mutations are caused by RDRP, resulting in immunologically similar HA/NAs (to previous strain), so Abs maybe can neutralize them

antigenic shift: new virus strains with HA/NA that are immunologically DISTINCT. changes come from genetic reassortment of previously circulating human and animal influenza viruses.

sometimes host cells can be infected with 2 diff infleunza viruses at the same time, and reassortment can happen then! (producing diff combinations of HA and NA genes)

PIGS as reservoirs: pigs are susceptible to both avian and human influenza strains, so they can get infect with both types and assortment can happen, and new strains develop. (mixing bowl)

VIRULENCE:most strains onlykill compromised ppl. but a few strains have been deadly to healthy individuals (1918 pandemic)

PREVENTION:

vaccines:can be cultivated in embryonic eggs, so new vaccines are produced by genetic reassortment to produce a strain with desired HA. its made inactivate by formaldehyde.

virus in cells can be detected by agglutination

types of vaccines: WV (whole) SV (subvirion, where the envelope is solubilized), and SA (surface antigen)

Antiviral Drugs:plug drugs, which target a highly conserved site on NA, so the end of infection cycle is blocked.

nuf nuf nuf.