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What is a virus?. Obligate intracellular parasiteSmaller than bacteria: 20-450nm, unique mode of replicationComposition:Nucleic acid: DNA or RNA, linear or circular, monopartite or segmented, ds or ss, ve or ve polarityNucleocapsid: genome protein coat surrounding it: protects genome whilst in transitLipid envelope: help viruses enter host cells.
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1. MICROBIOLOGY
2. What is a virus? Obligate intracellular parasite
Smaller than bacteria: 20-450nm, unique mode of replication
Composition:
Nucleic acid: DNA or RNA, linear or circular, monopartite or segmented, ds or ss, +ve or ve polarity
Nucleocapsid: genome + protein coat surrounding it: protects genome whilst in transit
Lipid envelope: help viruses enter host cells e.G HIV is segmentede.G HIV is segmented
3. Classification ICTV classification: Order, family subfamily, genus species
Baltimore classification: basically, how they make mRNA
-ve sense RNA is complimentary to mRNA so needs to be converted to sense strand first so its then replicated-ve sense RNA is complimentary to mRNA so needs to be converted to sense strand first so its then replicated
4. Measurement of viruses By observing disease in host
Plaque assay: Infection of susceptible host cell, replication, release and infection of new cells. Area of killed cells large enough to be seen = plaque. Titres expressed as plaque forming units/ml
Electron microscopy
Polymerase chain reaction
Immunological evidence of infection
5. The Steps that cause disease Binding
Virus surface proteins bind cell receptors
Penetration
enveloped ? fusion at cell surface
non-enveloped ? genome/core passes through
Eclipse phase
Virus proteins expressed
Nucleic acids replicated
Assembly
Release (cell lysis or budding)
Latent period in HASV 10 hours, in eclipse phase no infectious particles presentLatent period in HASV 10 hours, in eclipse phase no infectious particles present
6. Latency Herpes viruses, e.g. HSV or varicella zoster virus (VZV)
After lytic infection viruses enter neurones and genomes are maintained as circular DNA (episomes) in nucleus
May reactivate years later to cause recurrent infections
E.g. cold sores, HSV; shingles, VZV
7. INFLUENZA
8. Influenza... Helical nucleocapsid
13.6kb
RNA Ss ve
8 segments
enveloped
9. A bit about Haemagglutinin Trimer, binds to sialic acid
Each monomer has HA1 and HA2 (contains fusogenic peptide)
10. Method of Replication
11. Relenza, Tamiflu http://www.pharmasquare.org/flash/Tamiflu.html#RNA
This blocks the virus from disseminating..
Neurominidase removes sialic acid so the virus can be removed
12. How do we get new epidemics Antigenic drift: radical change of surface proteins
Antigenic drift: point mutations small change in surface proteins
13. Bird Flu Very high mortality in man
Spread from migrating birds to other birds and to man
No spread from man to man discovered
Dont get too happy ... Still a huge threat
As can adapt better to humans: better binding, replication, transmission and escaping immune system
14. How it can adapt.. Binding: Binds better to a2-3 than a2-6, a mutation can change a2-6 to a2-3
Replication efficiency: Avain flu polymerase has glutamic acid at 627 of PB2 (poor rep in humans), Human flu has lysine, efficient avian flu has lysine instead.
Escape immunity: NS1 confers resistance to interferon mediated inhibition of influenza virus replication, avian NS1 becomes more resistant to human interferons
15. Virus Immune evasion Antigenic variation:
Hiding: establish a latent infection in which virus proteins are not expressed, so infected cell may not be recognised by immune system e.g herpes
Express proteins that inhibit the immune response:
Block antigen presentation via class I MHC
Block recognition by NK cells
Secrete proteins to capture cytokines, chemokines or
interferons
Block intracellular signalling pathways, or apoptosis
16. Interferons Help us fight viruses
Many viruses interfere with them
Viruses evolve, then we evolve, then they evolve again etc
Just gonna explain geoffs slides...