Heamophillus Influenza Flashcards
Structure
1) spherical : 80-120nm
2) polymorphic, long filamentous forms - during early passages of new isolates
3) genome: (-) ss RNA –> 8 seperate a segments (a&B) type
7 separated segments (c types)
4) enzyme transcriptase RNA dependant RNA polymerase
5) M protein : Matrix
6) Capsid: 8 nucleocapsid fragments, helical structure
7) super capsid
: virus encoded GP into envelope
-HA- Haemaglutinin
-NA- Neuraminidase
Antigenic structure
1) HA: represents 25%viral proteins (400-500 molecules) - length 14nm,trimmer ( imparts greater stability)
i) HA1- monomer
ii) HA2 - dimer
Virus
-Orthomyoxoviridae influenza virus
- 3 types
- A,B,C
-type A : ( AG changes !!)
Host: human, birds, pigs, horses, seals
Causes: epidemics&pandemics (1918-2mil dead) -Spanish flu
-Type B: (AG changes lesser)
Host: human sometimes causes epidemics
-type , ( Ari for children )
Host: sporadic form, mild disease
-general: 19th haemophilus influenza
-isolated in 1933
HA structure
- elongated stalk ( base anchor in membrane)
- capped by a large globule
- pocket located at the too of the globe cellular receptor binding site ( the pocket is inaccessible to AB )
- trimmer HA : non infectious –> cleavage if HA1 and HA3 necessary for virus particle to be infectious ( by cellular protease)
Structure of HA gene
-14 alleles encode 14 serological independent , non cross reacting HA subtype h1-h14
Three subtypes
- recovered from human H1, H2, H3
- results in appearance of a new subtype
- mechanism for AF shift–> genetic re-assortment between humans and no humans ( especially of avian origin)
Functions of HA
1) viral adhesion
2) enhance
The fusion of viral and host cell membrane
3) haemogluttinates RBC (human, chicken, guinea pig)
4) determines production of neutralizing AB–> humoral IR
Antigen structure : NA
- cleaves mucin( protective barrier of resp ep allowing HA to attatch
- 5% viral proteins (150mol£ 6nm length
- spike is tetremer, composed of 4 identical
- Monomers:
- slender stalk
- box shaped head
- catalytic site for Neuraminidase on top of each head ( 4 active sites)
Function of NA
At end of viral cycle
- facilitates releaser of virus particles from infected cell during budding
- prevents self- aggregation of virions
NA gene
- 9 alleles encode 9 serotyoes
- independent NA subtypes
- human A virus 2 NA - N1,N2
NA is target for antivirals:
- zanamivir
- Oseltamivir
NP internal protons
9 NP - capsid proteins
- determine the type of specified
- determine intoxication symptoms
M proteins (40%)
- M1 –> between capsid and super capsid
- M2–> ion channel protein ( fewer copier per particle)
- target for Amantadine, remantadine
Pathogenesis : AG changes
1) Antigenic drift
- minor AG changes because of point mutation in the gene–> amino acid changes in the protein
( virion can escape recognition by hosts immune system)
2) Antigenic Shift
- Major AG changes in NA and HA –> results in the appearance of a new subtype
- The mechanism for AG shift is genetic re assortment between humans and no humans ( especially if avian origin)