Biochemistry of Swine Flu. SMPatel

Transcription

1 Biochemistry of Swine Flu SMPatel

2 Clinical Features Great overlap among Common cold Seasonal Flu Swine flu Bird Flu Laboratory tests are only way to differenciate them

3 ClinicalFeature Common Seasonal Cold Flu Fever <100'F >100'F Headache, Bodyache Weakness Running nose, sneeze, Sore throat Spread Sinus, Bronchi, Middle Ear Lung

4 ClinicalFeature Swine Flu Seasonal Flu GIT Spread Bronchi, Lung Spread Diarrhea, Vomiting Pneumonia Bronchitis Enchephelitis

5 What is the reason for difference in clinical features? Man are collection of molecules Swine flu viruses are collection of molecules They react with each other The answer lies in understanding molecular interaction between them

6 Major causative organisms Common cold Rhinovirus Swine Flu Seasonal Flu Influenza virus

7 Stucture of Influenza Virus Electron Microscopy

8 H N Stucture of Influenza Virus Capsid and membrane

9 Major causative organisms Common cold Swine Flu Seasonal Flu Rhinovirus Swine origin Influenza virus S-OIV Human origin Influenza virus H1N1 H3N2

10 Hemagglutinin Trimeric Sialic acid binding sites (3)

11 Sialic acid binding sites (3) HA Top View

12 What the hell is sialic acid? It is a monosaccharide It is neuraminic acid derivative It is present in glycoprotein It is present in glycolipids GP, GL are present on cell surface

13 Neuraminic acid

14 Anomers of Neu

15 Neuraminic Acid + Various Groups =Sialic Acids Diversity in the sialic acids Neuraminic Acid Essentials of Glycobiology Second Edition Acetyl, Methyl, Sulphate, Phosphate, Glycol -O(CH2)2OH Chapter 14, Figure 2

16 What the hell is sialic acid? It is a monosaccharide It is neuraminic acid derivative It is present in glycoprotein It is present in glycolipids GP, GL are present on cell surface

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18 Oligosaccharide chain with Sialic acid Such chains are bound to membrane protein/lipid forming Glycoprotein and Glycolipid

19 Hemagglutinin Trimeric Sialic acid binding sites (3)

20 Sialic acid binding sites (3) HA Top View

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22 Virus is phagocytosed phagolysosome is formed

23 Oligosaccharide chain with Sialic acid There is glycosidic bond between Terminal sialic acid and adjesent Galactose

24 Respiratory Stomatch Intestine Brain Upper respiratory

25 H1, H5 H3

26 ClinicalFeature Swine Flu H1N1 Seasonal Flu GIT Spread Bronchi, Lung Spread Diarrhea, Vomiting Pneumonia Bronchitis Enchephelitis H3N2

27 Lactins Lactins are proteins for which receptor is carbohydrate Hemagglutinin is a protein It bind to carbohydrate receptor on surface Hemagglutinin is a lactin

28 H+ Virus is phagocytosed phagolysosome is formed

29 HA inside phago-lysosome does not sit quiet- fusion peptide Hydrophobic Longest alpha helix known

30 Hydrophobic fusion peptide is inserted in to phagosome membrane

31 1 2 Fusion peptides clump together, Allow RNA to exit

32 M2 ion channel allow H+ in virus core M2 Ion channel H+

33 Acidic core dissociate RNA from RNAP H+ M1 + RNA

34 Fusion peptide(he), M2 M2 remove protein from RNA Fusion peptide(he) open viral core to cytoplasm Both together cause exit of RNA from Phagosome

35 Amantadine prevent release of RNA from RNA-P in phagosome M2 ionchannel in viral Capsid and envelop Rx M2blocker Amantadine Rimantadine Resistance

36 Neuraminidase Protein-Oligosaccharide-Sialic acid Protein-Oligosaccharide + Sialic acid

37 ll Ce in Muc Why virus need neuraminidase ion has ad Clump

38 Why virus need neuraminidase Mucin have sialic acid Cell surface have sialic acid Clump Cell adhasion Hemagglutin itself is a glycoprotein with sialic acid

39 in Muc Why virus need neuraminidase Clump Cell adhasion

40 Neuraminidase Removal of virus from sialic acid rich mucin of respiratory tract Hemagglutinin is sialo-glyco-protein So Virus can bind each other via their own H and Sialic acid This aggregate virus when released from cell released virus also bind same cell

41 in Muc Why virus need neuraminidase Clump Cell adhasion

42 N vs H Sialic acid is receptor for H Sialic acid is substrate for N Too much H will allow entry, but not release (normally 80% protein on surface) Too much N will remove cell-surface sialic acid, preventing virus entry N-inhibitors will tilt balance by preventing release of new virus from the cell

43 Neuraminic acid analog Laninamivir Oseltamivir Zanamivir Peramivir Rx Neuraminidase inhibitors

44 Rx Neuraminidase inhibitors Do not kill virus Do not prevent virus entry in cell Do not prevent its replication in cell It clumps virus in ECF, on cell surface decreased diffusion from production site to other place in body Only prevent spread from cell to cell

45 N vs H Mutation in Neuraminidase may decrease viral release Escape-mutation may occur in Hemaglutinin, to decrease its affinity to sialo-protein on cell surface

46 There are 8 RNA molecures in each virus

47 Influenza A and B viruses carry two surface glycoproteins, the haemagglutinin (HA) and the neuraminidase (NA). Both proteins have been found to recognise the same host cell molecule, sialic acid. HA binds to sialic acid-containing receptors on target cells to initiate virus infection, whereas NA cleaves sialic acids from cellular receptors and extracellular inhibitors to facilitate progeny virus release and to promote the spread of the infection to neighbouring cells. Numerous studies performed recently have revealed that an optimal interplay between these receptor-binding and receptor-destroying activities of the surface glycoproteins is required for efficient virus replication. An existing balance between the antagonistic HA and NA functions of individual viruses can be disturbed by various events, such as reassortment, virus transmission to a new host, or therapeutic inhibition of neuraminidase. The resulting decrease in the viral replicative fitness is usually overcome by restoration of the functional balance due to compensatory mutations in HA, NA or both proteins

48 Get Swine Flu to servive against humans

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