C replicative cycle Flashcards
- Attachment
recpetor binding pocket of HA1 binds to N-acetyl neuraminic acid (NANA) aka sialic acid. it is terminal sugar of many glycoproteins the binding of HA to NANA has low affinity, binding of multiple HA to multiple NANA has high avidity
- diff serotypes of influenza have diff
aa residues lining the receptor binding pocket. these recognize diff linkages of NANA. for eg human influenza virus the NANA is linked to galactose by an alpha (2,6). avian influenza virus the NANA is linked by alpha (2.3)
as well as affecting host range, diff affect tissuetropism
avian strains replicate in the intestines of the bird. human strains replicated in the respiratory tract only
- entry and uncoating
virus is taken up by endocytosis. endosome has prton pumps. decrease in pH in endosome causes HA2 to form a long extended alpha heliz w.the fusion peptide at the end. fusion peptides insert into endosomal membrane. HA1 pushed to sides
- entry and uncoating
HA2 separate bringing the endosomal membrane toward the viral envelope. the membrane fushes
- entry and uncoating
as pH of endosome decreases M2 ion channel is activated. protins now enter into envelope. decrease in pH causes a conformation change in M1, the genome segments released into cytoplasm
- role of the cells nucleus
most RNA viruses are replicated in cytoplasm. influenza unusual b/c rna synthesis occurs in nucleus
- fn of nucleocapsid proteins
have a sequence called nuclear localization signal, normal host cell signal used to transport proteins like DNA and RNA pol into nucleus
- what are genome segments coated with
nucleocapsid proteins
- how does influenza virus exploit nuclear localization signal
gets 8 nucleocapsid and attach P complexes into the nucleus
- mRNA synthesis
in the nucleus the mRNA is synthesized early in the infection
- what is the P complexes composed of
3 subunits. PB1 is a cap dependent RDRP. PB2 is an endonuclease. PA is a cap independent RDRP
- mRNA synthesis uses
PB1 and PB2 only
- PB1 requires a
primer
- fn od PB2
cuts of the cap and 10 nucleotide from host mRNA. called cap stealing. means host mRNA won’t be translated
- mRNA synthesis
PB1 uses the primer to synthesize +ive strand mRNA. when gets to u7 region is stutters, producing poly-a-tail. last 20 nucleotide are missing so new +ive strand cannot be used as RI
- protein synthesis
mRNA transported into cytoplasm where it translated. P complex, NP, and M1 proteins are transported into the nucleus. HA, NA and M2 are synthesized on the RER and then inserted into the cell’s membrane
- genome synthesis
as the [] of NP increases in the nucleus the P complex changes fn. PA is used instead of PB1 and PB2. PA does not need a primer it produces full length +ive strand RNA that does not have a cap or poly-a-tail
- how is -ive strand genome segments synthesized
+ive strand RI can be used by PA to synthesize -ive strand genome segments
- fn of NP
new segments are coated with NP. NP forms a helical capsid. segments are associated w/the newly synthesized P complexes and M1
- Assembly/exit
the M1, P complex and NP leave the nucleus. M1 interacts w/inner domain of HA and Na that are already inserted in the PM. each segment has a specific packaging sequence which ensures that one copy of each segment is packaged
- how does influenza virus exit
by budding
- maturation
both HA and NA are glycosylated. terminal sugar is NANA/sialic acid. if released like this visions would stick together and to cell they were exiting form. NA cleaves NANA allowing it to be transmitted to another person/cell
