Lecture 13 Flashcards
Influenza
one of most common reasons for people to seek medical care.
-all exposed to/have experiences of
crosses boundary of community, secondary and sometimes tertiary
(community/primary care during mild cases. Influenza epidemic many require hospital/secondary care. Ventilation support/extra-corprial-membrane oxygenation/Quaternary Care
Levels of care
Community/Primary care: Mild cases
Hospital/Secondary care
Tertiary
Quaternary
Upper respiratory tract symptoms
Antibiotic Augmentum: ceflasporin antibiotic, works same as penicillin, with different structure (comes from a different type of mould)
Knowing these symptoms: minor viral illness? potentially serious: influenza A or B? (these conditions will get better on their own) Bacterial condition: Pneumonia, which requires specific therapy?
“runny nose for 2 days and sore throat”- probably just a cold (many viruses cause colds)
Why influnza?
Ubiquitous in human populations
-Influenza A is a zoonosis (virus of animals- primarily birds. Humans are an incidental host)
Very common cause of illness
common cause of death (winter. primarily frail elderly people, who due to other illnesses, live in hospitals/rest homes. Also per winter will kill a young/healthy person, often have underlying problems)
epidemics-threat of pandemics - swine flu
Large social/financial impact (hospital hard as medical staff are off sick)
Model for recurrent infection despite development of immunity (wont catch chickenpox after initial bout of it (Herpes/variscella zosta virus stays in you lives in sensory nerve roots of dorsal root ganglia in the spine. May wake up when 60-70, crawl down sensory nerve and cause shingles. - Shingles is a patch of chickenpox associated with peripheral nerve (if trigeminal nerve, will occur on forehead, sometimes nose or eye. If thoracic nerve, will be in a band across one side of the chest). Reactivation, but primary illness of chickenpox will only be caught once. If really really damaged immune system, chicken pox may occur again, but only in haematology unit where people are receiving cancer treatment)
Influenza as a virus
Influenza does escape immunity
Influenza is a Respiratory virus
-may not share structural properties. Transmission spread by dropelt route (respiratory virus). Causes respiratory illness
-Orthomyxoviridae
-envelope derived from host cells (bud off cell, dont lyse and rupture)
-envelope glycoproteins of critical importance in virus entry and egress from cells
-single-stranded RNA negative sense virus
Influenza A, B and C - related. (C may cause cold symtoms in some people but not alot of evidence) - Primarily concerned with A and B
Influenza structure
RNA segmented 8 genes - easier for 2x unrelated influenza viruses to share their genome. easily swapped
Envelope with virus proteins (neuraminodase and hemagluttin) on their surface - important in regards to immunity
Influenza A
Bird virus- many types in wild
-can be non-pathogenic (infect fllock of geese without illness) - mostly called “lowly pathogenic avian influenza virus” giving GI gastrointestinal illness to some members of the flock (primarily binds to these cells) - if poulty/egg laying flock, these birds may no lay eggs as well for a period of time. “highly p.a.i.v”-bird flu. describes capacity to kill birds (not humans)
humans are “incidental” hosts
causes epidemics and pandemics
lots of subtypes
-defined by surface glycoproteins: Haemagglutinin and Neuraminidase
-strains named by H and N type and place/year of origin
-A/H1N1/ Mexico city 2009 “spanish flu” H3N2 and H2N2 have also circulated in human populations. 16 H types and 9-10 N. Therefore large potential combinations
-8 genes. 10 viral proteins (M2 protein, old influenze viral drug (Amantadine) target, ion channel allowing RNA to be uncoated and released. useless drug, had neurological side effects. now only used to settle behaviours of people with severe brain injuries)
-Hemagglutinin (H) - viral attachment to cell membrane sialic acid
- Neuraminidase (N) - cleaves H from sialic acid as virus leaves host cell
-M2 proteins- ion channel that opens viral core
Influenza B
a Human virus
Causes epidemics but Not pandemics (no new types that humans arent a little immune to)
No subtypes
-only 1 type of Hemagglutinin and Neuraminidase (evolve but only 1 type)
-strains named after year and place of origin e.g. InfluenzaB/Shanghai/2005
Replication cycle of influenza viruses
Typical cell cycle
1. Coated pit- virus must interact with cell
2. coated vesicle
3. endosome - virus must be opened up. M2 protein. (amantadine drug interferes with this)
Genome segmented and passed into cell nucleus
4. ribosomes and RER rough endoplasmic reticulum
5. nucleus. mRNA synthesis. RNA replication
6. translation –> mRNA –> NP, P
7. mRNA
8. membrane proteins
9. Synthesis and glycolisation of envelope proteins on Golgi apparatus - lots of H and N and new capsid proteins
10. Completion of glycolysation of envelope proteins. Insertion of envelope proteins into plasma membrane
11. Budding- taking host cell membrane with it (the envelope of the virus)
Seasonal Influenza
a.k.a. influenza epidemic
-AH1N1 (first 1918, more than died in WW1, military camps. worst pandemic of modern history. mostly younger people. readily spread/ spanish flu. adults(over 45) fine as believed to have been prior pandemic in 1880 where survivors had immunity-less effected) (2009, strain recombined, took RNa from other viruses, sufficiently different now to cause pandemic effecting) 10% of population; AH3N2 and B (3x circulating human influenza strains)
-in temperature zones ‘flu season is winter (sometimes Northern hemisphere in Jan-Feb. Southern hemisphere Jun-Sept) (opposite in 2009 pandemic)
-tropics - all year (still fluctuates, but no seasonality.)
Infection of respiratory epithelium
-occasionally other sites (e.g. conjunctive)
-no viraemia or invasion
Illness lasting 5-6 days
-severe but not life threatening (high fever)
-3-4 days in bed, off work
Mortality in young and elderly, chronic lung disaese etc.
Approx 20% children and 5% adults affected each year
Recovery with immunity
Influenza epidemics occur each year
No influenza circulating in summer
- winter epidemic 6-8 weeks/brief seasonal epidemic/high spike
- people now immune to this strain
- most people in summer have cold- but if similar symptoms and Fever (hallmark symptom) is actually probably flu
- diagnosis clinical but somewhat depends on time of year
If recovery from influenza infection results in immunity- how do we get further infections and epidemics each year?
Immune to that specific strain (that winter or following winter)
-may get sick in a few years
- RNA virus has no proof reading capacit. when it replicates it may make mistakes. some terminal, but sometimes changes a structure of protein
-we have antibodies which protect us. but viruse may reach a point where antibodies may be no longer able to neutralize Hemagglutinin/stop binding to respiratory/epithelial cells
= Antigenic drift (virus slowly relentlessly changing over time) - Influenza A and B are laways undergoing antigenic drift
-surface glycoproteins (primarily H haemagluttinin) continuously mutate and change
-immunity is mediated by mucosal (and humoral) antibody response
-after considerable mutation the antigen structure can be sufficiently different and escape the immune systems memory
-generally child is susceptible to influenza as dont have full immunity (2-4 years) adult 7-8 years. No person is truely immune to flu.
-as get older, Infleunza frequency does decrease
Haemagglutinin
Attachment firmly of Haemagglutinin to sialic acid allows entry into cell
sialic acid (residues on epithelial cells-nose, back of throat, trachea, large bronchi)- what influenza hits as you breath it in
ubiquitous on cell surface membrane
-past infection with a similar strain of virus - IgA antibody to hemagglutinin present: Infection prevented (neutralizing/prevent binding)
Antibody to H1 will completely prevent H! bindging to sialic acid and may reduce the binding of H1 and to different degree reduce the binding of H!# to sialic acid
-This results in partial immunity to closely related strains of influenza virus- maybe minor illness or no symptoms at all
-Minor alterations in the Hemagglutinin may prevent antibody attachment - this “new” strain can cause infection
Neuraminidase
Main influenza drug is a Neuraminidase inhibitor
As influenza buds off the host cell (epithelial cell) haemagglutinin remains stuck to the cell (cannot go on and infect if inhibiting N drug is present)
-but if you dont get N inhibiting drugs early on in the infection, you will already have flu infecting cells, is too late (useful early on/need from the outset of infection)
Neuraminidase leans over and cleaves sialic acid “receptor”
The virion is now free to go and infect another cell
Antigenic Drift
Minor changes in antigens continuous process leads to repeat infection with -Influenza A H3N2, AH1N1 and influenza B on average a child will have influenza every 3rd-4th winter an adult every 10th winter
