Influenza is a common viral infection of the upper respiratory tract caused by influenza viruses types A, B, or C. Type A is the most virulent and is commonly associated with human disease. The 1918 flu pandemic killed over 50 million people worldwide. Seasonal flu epidemics affect hundreds of thousands annually. The virus is spherical with RNA segments and surface proteins HA and NA that allow attachment and entry into host cells. It is transmitted through droplets from coughing/sneezing or surfaces. The virus infects respiratory cells and hijacks the cell to replicate then buds and spreads. Symptoms result from both viral infection and immune response. Most recover in 1-2 weeks but some develop pneumonia. Treatment focuses on relieving symptoms

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INFLUENZA
 Influenza
Influenzaorfluisa commonviral disease of the upperrespiratorytract.There are three typesof
influenzavirus:A,Band C. Major outbreaksof influenzaare associatedwithinfluenzavirus typesA orB.
Infectionwithtype Binfluenzaisusuallymilderthanwithtype A.InfluenzaCiscommonbut rarely
causesdisease.InfluenzaA isthe mostvirulenttype andiscommonlyassociatedwithhumandisease.
Between1918 and 1919 fluis thoughtto have killedover50 millionpeople(6timesasmanyas diedas a
consequence of the WorldWar I).Thisglobal pandemicpossiblyinfected50% of the world’spopulation
and up to20% died.Itwas causedbyan unusuallypathogenicstrainof influenzaA virus. Otherglobal
influenzapandemicshave beenrecordedthroughhistoryandtheyseemtooccurevery10 to 40 years.
Each year,many countries,includingthe UK,experience seasonalinfluenzaepidemicsthataffect
hundredsof thousandsof people.
 What causes flu?
The influenzavirusparticle- virion- isusuallysphericalinshape andcarriesitsgeneticmaterial oneight
piecesof single strandedRNA knownassegments.Eachsegmentcarriesgenesthatencode forproteins
that the virusneedsinorderto replicate inside the infectedhostcell.The genome isprotectedbya
membrane envelope.Protrudingfromthe virusenvelope are hundredsof copiesof twodifferent
varietiesof viral glycoproteinspikes.Approximately80% of the spikesare haemagglutinin(HA) andthe
remaining20%are neuraminidase (NA).The HA andNA surface proteinsare involvedinviral attachment
and entryto hostcells.Theyare alsothe main part of the virusrecognizedbyourimmune systemas
foreign,andmostof the antibodieswe make afterinfectionare againstthese antigens.
The stages of cell infection of an influenza virus. The virus appears rounded in shape, with a
core of ribonucleic acid (RNA). It has a spiked outer coat which allows the virus to attach to
host cells. Host cell cytoplasm appears granular. At top frames (3 images) the virus attaches
to the cell, causing the cell membrane to fold around the virus. At lower frames (3 images) the
virus penetrates the cell, infecting it, and causing more influenza viruses to be produced. This
virus is contagious and invades mucus cells in the respiratory tract.

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 Transmission
The fluvirusis extremelycontagiousandistransmittedfrompersontopersonbydropletsexpelled
whensneezingandcoughing.Itcan alsobe transmittedbydirectcontact,for example bytouchingvirus-
contaminatedsurfacessuchasdoor handlesandthentouchingthe eyesornose.Goodhygiene
practices,suchas correct hand washing,are veryimportantinpreventinginfection.
 Infection and replication
Influenzavirusesinfectepithelial cellsinthe upperrespiratorytract(nose andthroat).If the infectionis
severe the viruscaneventuallyreachthe lungsandcause pneumonia.The respiratorytract’sfirstline of
defence isaprotective layerof mucus.The virusNA proteincancut throughthisenablingthe virus
particle toreach the epithelial cell surface.
The virusthenusesitsHA proteinto attach to a receptoron the hostcell’splasmamembrane andis
takenintothe host cell byendocytosis.The ribonucleoproteincore,thatcontainsthe viral RNA andthe
viral polymerase usedforreplication,isreleasedintothe cytoplasmandmovesintothe nucleus.Viral
RNA is replicated.
The host cells’ownribosomesare hijackedtomake proteinsfromthe viral mRNAs. New copiesof the
RNA genome are shuttledoutof the nucleusandup to the plasmamembrane where theycombine with
the newlymade viral proteinsandbudoutof the cell’splasmamembrane,acquiringtheirenvelope in
the process.Finally,usingthe NA proteintocut themselvesawayfromthe infectedcells,the new virions
move awayto infectothercells.
The host cellsare damagedwhentheybecome infectedbythe virus.The patient’simmunesystem
respondsbyreleasingchemicalscalledcytokineswhichstimulate leukocytes(whitebloodcells) totravel
to the site of infectionandfightthe virus.Mostof the symptomsare infact causedby the body’s
immune response.These include:
 High fever
 Chills
 Severe fatigue
 Headaches
 Muscular aches and pains
 Non-productive cough
 Sore throat
Whenthe NA proteinof influenzabreaksdown the mucusliningthe epithelialcells,thisalso leavesthe
cellsmore susceptible toinfectionby otherpathogens,suchasbacterialike Staphylococcus aureus
and Haemophilus influenzae.
 Treatment

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Most people recoverfromfluwithin1-2weeksbutmore seriousillness,andevendeath,canresultfrom
secondaryinfectionse.g.bacterial pneumonia.Thisismore likelyininfants,the elderly,peoplewhoare
immunocompromisedandthose withchroniclungdisease suchasemphysema.
There are twowaysof tacklingthe disease:treatingthe symptomsandattackingthe virus.The
symptomscan be alleviatedwithdrugstoreduce feverandpainsuchas paracetamol.Antiviraldrugs
can be effective againstinfluenzabutmustbe administeredwithinthe first2days of symptoms
appearing.Drugssuchas oseltamivir(Tamiflu®) attackthe virusbyinhibitingthe enzymeneuraminidase
and therefore preventthe virusfrominfectingcells.
Antibioticsare notusedtotreat influenzabecause theyworkbyinhibitingbacterialcell wall production
and proteinsynthesisandblockcell metabolismandhave noeffectonviruses.Theycanbe usedto treat
secondarybacterial infections.
 Vaccines
Antibodiesthatrecognize the HA andNA surface proteinsof the influenzaviruscanprotectus from
infectionbystoppingthe virusreachingthe hostcell surface.Thismeansthatpeople will notbe infected
by the same strainof influenzaaftertheyrecoverfromflu. Givingasmall dose of acrippledstrainof
influenzavirusoran injectionof purifiedHA proteinasavaccine,can stimulate the immunesystemto
make antibodiestoHA to protectus fromflu.
 Coldor flu?
The terms cold and flu are often used interchangeably but they are in factdistinctdiseases caused by very
different viruses.A cold is caused by several groups of viruses;the most common is rhinovirus and usually lasts
between 2 and 4 days.Symptoms includerunny nose, sneezing and mild fatigue. Flu is much more serious than a
cold.Symptoms may lastfor a few weeks and the illnesscan bemuch more debilitating.If in doubt, remember the
£50 test: if a £50 note is pinned to your front door and you areincapableof dragging yourself out of your sick bed
to collectit…you have the flu. If the thought of free money puts a springin your step…it’sjusta cold!
 Flu epidemics and pandemics
The influenzavirusgenesare made of RNA and are more prone to mutationsthangenesmade of DNA.
Influenzavirusesundergoconstantgeneticvariation.
 Antigenic drift
Influenzavirusesare changingbyantigenicdriftall the time.Mutationsinthe genescodingforthe
proteinsNA andHA resultinminorchangesto surface proteins.If the HA antigenchangesshape then
the antibodieswon’tbe able torecognize itandbindtoit.The newlymutatedviruscanthenbindto
receptorsonthe host cell andinfectit.
Thisis whyitis possible foranindividual tobe infectedmore thanonce withinfluenzaandwhythere is
a global surveillance teamthatmonitorsthe evolutionof humaninfluenzastrains.Everyyearanew
strainof virusemergesandthe vaccine mustbe updatedsothat the antibodiesitinducesare agood
match to the antigensof the strainsthat are circulatinginthe community.

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 Antigenic shift
Thisoccurs in influenzaA virusesonlyandisdue tothe reassortmentof RNA segmentsfromtwo
differentviral strainsinfectingthe same cell producingvirusesthathave entirelynew antigens.Wild
birdsgetinfluenzainfectionsall the time.Sometimesthese avianvirusesspreadtochickensandcause
outbreaksof ‘birdflu’thatcan devastate poultryfarms.
Most birdfluvirusescannotinfecthumans.Itisthoughtthat mostnew strainsof fluoriginate inChina
where manypeople live incrowdedconditions,ofteninclose contactwithdomesticatedpigsandbirds.
Birdscan transmitinfluenzatopigs.Pigscantransmitthe virusto humansand vice versa.
Recombinationof humanandbirdstrainsinside pigscanresultin novel strainsof influenzaA thatwill
infecthumans.Withthe increase inglobal transportandurbanization,epidemicscausedbythese new
strainsare likelytospreadrapidlyaroundthe world.
Theoreticallythese epidemicscouldbe controlledbyimmunisation,butanew vaccine mustbe
producedforeach newstrainof flu,so vaccinesmaynotbe immediatelyavailable inthe threatof an
epidemic.The WorldHealthOrganization(WHO) hasdevelopeda‘global influenzapreparednessplan’
whichadvisescountriesonhowtoprepare forthe possibilityof anpandemic.Thisinvolves:
 Rapiddetectionof unusual influenzaoutbreaksandisolationof possible pandemicviruses
 Measuresto preventspreadof the disease,including:publichealtheducation,travel andtrade
restrictionsandquarantine procedures
 Rapiddetectionof unusual influenzaoutbreaksandisolationof possible pandemicviruses
 Measuresto preventspreadof the disease,including:publichealtheducation,travel andtrade
restrictionsandquarantine procedures
 The unpredictabilityofpandemics!
The WHO ison constantlookout forthe firstsignsof a pandemic.Forsome yearsthere hasbeenpublic
concernthat a strainof avianflucalledinfluenzaA H5N1 will mutate intoaformthat is easily
transmittedbetweenhumansandcause apandemic.The virusoccursin bothwildanddomesticated
birdswhere itis transmittedinsaliva,faecesandnasal secretionsandhasa highmortalityrate.A small
numberof humans have contractedthisstrainof bird flu,mainlybyclose contactwithpoultry,andby
July2009 the WHO had confirmed436 cases and263 deathsworldwide.Currentlythere isverylimited
humanto human transmissionof the virus.
In April 2009 scientistswere surprisedbythe emergence of anovel influenzaA H1N1 (2009) virusfrom
Mexico.Popularlycalled‘swine flu’,the straincontainsacombinationof geneticmaterial thatistypical
to avian,swine andhumanfluviruses.Itspreadveryrapidlyaroundthe world,causing11,000 cases in
42 countriesinthe first4 weeks.On11 June 2009 the WHO declaredthe firstglobal flupandemicfor40
years.The pandemicwasofficiallydeclaredoverinAugust2010 althoughthe straincontinuedto
circulate.

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The H1N1 (2009) strainwas includedinthe 2010/2011 seasonal fluvaccine alongwithtwoother
influenzastrains.The H1N1 (2009) virusisexpectedtocontinue tocirculate asa seasonal influenza
strainfor the foreseeable futureandbecause of this,more peoplewilldevelopimmunitytothiscurrent
versionof the virus.However,the virusisalsoexpectedtochange overtime,meaningthatimmunityto
thiscurrentstrain maynot protectagainstfuture strainsof the virus.Global influenzasurveillance will
continue totrack the evolutionof H1N1 (2009).
Preparedby Amjad Khan Afridi
15/01/2016