EmilyVincent

Biology1615
4PM
Inthisscientificarticle,theauthorbeginstalkingabouthowdiseasetolerance
anddefinesitasevolutionarystrategyofhostsagainstpathogens.Thegroupthen
decidedtoinvestigateifthetoleranceofHIVinhumanswasassociatedwiththe
polymorphisminthehumangenome.Theauthorthengoesontoexplainthathost
populationscanappeartoways.Oneisresistancetothedisease,andthesecondis
tolerancetothedisease.Bydisentanglingthetwo,scientistsaregoingtobeableto
understandthecoevolutionbetweenhostsandpathogensmoreclearly.Investigating
thetoleranceandresistancewithHIVwasagreatoptionoftheauthorbecauseit
reaches
alevelintheplasmaofinfectedindividualsthatisapproximatelystableover
severalyears.HIV,likeotherdiseases,havearateofdiseaseprogression.Duringthis
phase,thegroupwasabletomakeobservationsandanalysis.CD4cellsinthebody
areabout1000peraverageperson.
TheauthoruseddatafromtheSwissHIVCohortStudy.Thereweremorethan
18,000enrolledHIVpositiveindividuals.However,forthisstudytheauthorshowsthat
theytooksomepeopleoutoftheirstudy.IftheCD4countwasavailable,thenthey
wantedtousethoseindividuals.Thestudydidnotincludeindividualswhowere
undergoingantiretroviraltreatmentbecausethatseriouslyalterstheCD4cellcount.
Afteralltheserestrictionsandinclusionswereapplied,thestudyturnedouttobeabout
3,000individuals.Betweenthemall,thereweredifferentalleles.FromHLAAtoHLAB

andC.Aftergettingtheinformationforthecelldecline,theauthorwasabletoshowhow
theyanalyzedtheinformationstatistically.Inthearticle,therearemanyequationsthat
showtheresults.Themostcommonequationsusedweretoshowthechangeinthe
CD4levels.Thefirstonebeingiftherewasonlyonefactoroftoleranceandtheother
wasifthereweremorethanonefactor.
TheresultsweredeterminedbythesetviralpointsandtheCD4count.The
declineintheCD4countshowedtheHIVinfectedindividuals.Firstfindingthe
relationshipbetweenthesetviralpointsandtheCD4count,theauthorshowedthatit
wasverynonlinear.Insteadtheresultsseemtobesomewhatmorequadratic.The
resultsofthisquadraticmodelgohandinhandwith5%oftheCD4+Tcelldecline,in
theindividuals.Thiswouldhavebeenconsistentwithpreviousstudiesinvestigatingthis
relationshipwithlinearmodels.Theauthorexplainshowtheytestedtoseeifthe
tolerancewouldchangewithage,sex,orage.Theonlythingthatwasaffectedwasthat
a60yearoldismorelikelytogetinfectedthana20yearold.Thentheywentontosee
iftherewasassociationwiththedifferentHLAallelesBandC.Howevertherewasnot,
butitdidshowthatthedifferentvariationsofHLABhadhighertolerance.Thisis
becausethereisaveryfastrateofdecliningCD4cells.
Thiswasthefirstformalanalysisoftoleranceinahumaninfection.Itwas
interestingthattherewasnoassociationwiththegendersbecauseinpaststudiesit
wassaidthatwomenwouldhaveahighertolerance.HLABalleleshadthemost
controllinginfluence.Especiallytheheterozygotes.Itshowsthatthedeclinebetween
thesetviralpointsandtheCD4cellsisweak.Morestudiesshouldbedonetohelp

understandtheassociationofCD4levelsandsetviralpointsbecauseasofnowthey
cannotbeseenasmorethanindependent.