epigenetics from hiv to immunizationchristl-meyer-science.net/images/pdfs/challenging... · barbara...
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EpigeneticsfromHIVtoImmunization:NewProspectsonHealthandDisease
1ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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„NothinginBiologymakessense,exceptinthelightofevolution“Thisisfroma1973essaybytheevolutionarybiologistandRussianOrthodoxChristianTheodosiusDobzhansky,CriticisingYoungEarthcreationismandespousingEvolutionaryCreationism.(AmericanBiologyTeacher,volume35,125–129)
2ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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Overview1. Genetics,HIVandtheImmuneSystem2. Epigenetics3. MicrobesinEvolution4. Immunization5. WhatdoesitmeantobeHuman?
3ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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1. Genetics,HIVandtheImmuneSystem2. Epigenetics3. MicrobesinEvolution4. Immunization5. WhatdoesitmeantobeHuman?
4ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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GenesforproteinsRNAmolecules???
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Genomes:Coding,noncoding,repetitiveelements
PLANTandHUMAN:Bothharbourabout25.000genes
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Effect of the „kit“-gene
7ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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Example:Trisomie21(DownSynrom)
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Genduplication as the driving force behind Evolution
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OverhalfofourDNAcomesfromretro-transposons,geneticelementsthatindependentlymultiplyandspreadthroughthegenome(deKoningetal.,2011).
OnthemoveThemechanismsbywhicharetrotransposoncalledLINE-1duplicatesitselfandspreadsthroughthehumangenomearebecomingclearer.Martin.eLife2018;7:e34901.DOI:https://doi.org/10.7554/eLife.34901
Inmammals,aretrotransposoncalledLINE-1isresponsibleformostofthesemultiplicationevents,eitherduplicatingitselforlendingits’photocopying’machinerytoothergeneticelements. 11ChristlMeyer,AIDSResearch,Vienna/
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Barbara Mc. Clintock ( Nobelprice for Physiology and Medicine 1983) Transposons „jumping genes“
ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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13ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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Humansandchimpanzees,whichdivergedfromacommonancestorsome5millionyearsago,differintheirgenomesequencesonlyinabout1–2%.Provirusesfixedinthegermlinecanprovideuswithafossilrecordofviruseslongextinctinthepopulation.InhumanDNAonly2-3%ofthegenomearecoding.97%arenoncoding(formerlycalled„junkDNA“).ThisDNAmightbeinvolvedingeneregulationprocesses.Inhumans,thereareabout80.000provirusesortheirremnants,comprisingabout6-8%ofthegenome,orabouttwiceasmanyasgenes.JohnM.Coffin,ProfofMolecularBiologyandMicrobiology,TuftsUniversity:
„Thereismoreprovirusinusthanthereisusinus“.
14ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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TheHumanGenomeProjectdiscoveredourgeneticbackgroundbyreducingtheamountofproteincodinggenestoapproximately20.000andaugmentedtheRNAtranscriptions.
ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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1. Alvarez-DominguezJR,HuW,YuanB,etal.GlobaldiscoveryoferythroidlongnoncodingRNAsrevealsnovelregulatorsofredcellmaturation.
Blood.2014;123(4):570-581.2.SabinLR,Del´asMJ,HannonGJ.Dogmaderailed:themanyinfluencesofRNAonthegenome.MolCell.2013;49(5):783-794.
3.UlitskyI,BartelDP.lincRNAs:genomics,evolution,andmechanisms.Cell.2013;154(1):26-46.
4.BatistaPJ,ChangHY.LongnoncodingRNAs:cellularaddresscodesindevelopmentanddisease.Cell.2013;152(6):1298-1307.
5.BergmannJH,SpectorDL.Longnon-codingRNAs…..16ChristlMeyer,AIDSResearch,Vienna/
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AleksandraE.Kornienko,ChristophP.Dotter,PhilippM.Guenzl,HeinzGisslinger,BettinaGisslinger,CiaraCleary,RobertKralovics,FlorianM.PaulerandDeniseP.Barlow
“Longnon-codingRNAsdisplayhighernaturalexpressionvariationthanprotein-codinggenesinhealthyhumans“GenomeBiology2016,17:14,DOI:10.1186/s13059-016-0873-8.
17ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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Human Genome Nature 409, 860-921 (15 February 2001) / doi: 10.1038/35057062; Received 7 December 2000; Accepted 9 January 2001
Initial sequencing and analysis of the human genome Internationbal Human Genome Sequencing Consortium Eric S. Lander... ...Here we report the results of a collaboration involving 20 groups from the United States, the United Kingdom, Japan, France, Germany and China to produce a draft sequence of the human genome. ...Hundreds of human genes appear likely to have resulted from horizontal transfer from bacteria at some point in the vertebrate lineage. ...Dozens of genes appear to have been derived from transposable elements. ...large recent segmental duplications...much more frequent in humans...
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Amajorpartoftheimmunesystem:MHC-MajorHistocompatibility–ComplexandHLA-HumanLeucocyteAntigen–Systemgivenewinsightsontheco-evolutionofthespecies,particularlyofmammals(andprimates)withmicrobes.
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HLAisthemostgenedenseandvariableregionandisrelatedtohealthanddisease!
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HLA-sequencesonChromosome6
21ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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HLAclasses
22ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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6p21.31
23ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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24ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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HLA 6p21.3
„Virus“bindingsite 25ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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http://www.geocities.ws/chiakwongmin/HIV/HIV_photo-picture/
HIVModel
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27ChristlMeyer,AIDSResearch,Vienna/Austria,2018
Brummeetal
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28ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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29JOURNAL OF VIROLOGY, Sept. 2008, p. 9216–9227 Vol. 82, No. 18 0022-538X/08/$08.000 doi:10.1128/JVI.01041-08
Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute/Early HIV-1 Infection
Zabrina L. Brumme et al. Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
The so called mutation of the „HI-Virus“
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„Life has a tendency to plurality, being colourfully, to independence, simply to freedom. The totaliarian system demands monolithical unity, uniqueness and discipline.“ (Vaclav Havel, dissident and president – Charta 77 /Chech Republik) 30ChristlMeyer,AIDSResearch,Vienna/
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Whatwerealize
...andwhatishidden.
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HIVcannotbethecauseofAIDS–itisageneticfactorinevolution
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TheGAG„viralprotease“isunderpositiveselectivepressure
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„Darkmatter“ofthegenomemayplayamajorbiologicalroleincelldevelopmentandmetabolismincludingdiseaseslikecancer.
InvolvedaremanydifferentNoncodingRNAgenesthathaverecentlybeendetected.
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Questions(concerningtests):
1. Isthetestsaveandvalid?2.Doesearlydetectionprolongelife-span?
3.Doesearlydetectionimprovelife-quality?
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HIV-Test Insert:
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Western Blot Test
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What does this mean? If you are tested HIV-positive in Germany or Africa, you can fly to Australia or France with your Western-blot test result and be claimed HIV-negative only because of the different standards that are applied.
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Sayre,K.R.,Dodd,R.Y.,Tegtmeier,G.,Layug,L.,Alexander,S.S.andBusch,M.P.(1996),
False-positivehumanimmunodeficiencyvirustype1westernblottestsinnoninfectedblooddonors.Transfusion,36:45–52.doi:10.1046/j.1537-2995.1996.36196190514.xLow-riskblooddonors(PCRnegative)canhavefalse-positiveresultsonWBtests.Increaseddetectionofenv-onlyandp24/env-onlyWBsappearsrelatedtothe
enhancedsensitivityofnewerenzymeimmunoassaystogp41andp24antibodies.
KeithR.Sayre,MBA,ProductManager,AIDS/HepatitisBusinessUnit,OrthoDiagnosticSystems,Inc.,Raritan,NJ.RogerY.Dodd,PhD,Head,TransmissibleDiseasesLaboratory,AmericanRedCross,Rockville,MD.GaryTegtmeier,PhD,DirectorofResearch,CommunityBloodCenterofGreaterKansasCity,KansasCity,MO.
LynneLayug,MPH,MT(ASCP),TechnicalOfficer,NationalReferenceLaboratoryforInfectiousDisease,AmericanRedCross,Rockville,MD.SteveS.Alexander,PhD,PrincipalScientist,AIDS/HepatitisResearchandDevelopment,OrthoDiagnosticSystems.
*6MichaelP.Busch,AssociateProfessorinResidence,DepartmentofLaboratoryMedicine,UniversityofCalifornia,SanFrancisco;andVicePresident,ResearchandScientificServices,IrwinMemorialBloodCenters,270MasonicAvenue,SanFrancisco,CA94118-4496.
Articlefirstpublishedonline:28FEB2003
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The diagnosis (prognosis) of a serious disease can lead to disease and death – even if the person was not sick before.
This is called the NOCEBO-effect!
The contrary – the PLACEBO-effect is scientifically better examined and proven.
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“RPD[rapiddiseaseprogression]wasthreetimesmorelikelytooccurininfantsbornto[AZT]treatedmothers-comparedwith
findingsinuntreatedmothers.”deSouzaRSetal.EffectofprenatalzidovudineondiseaseprogressioninperinatallyHIV-1-
infectedinfants.JAcquirImmuneDeficSyndr.2000Jun1;24(2):154-161
"CombivirisclassifiedbytheFDAasapregnancycategoryCdrug.PregnancycategoryCmeansthatanimalstudieshaveshownanadverseeffectonthefetusandtherearenoadequateandwell-controlledstudiesinhumans"http://www.aidsmeds.com/archive/Combivir_1083.shtml
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ChristlMeyer,AIDSResearch,Vienna/Austria,2018
ComparisonsofCausesofDeathandMortalityRatesAmongHIV-InfectedPersons:AnalysisofthePre-,Early,andLateHAART(HighlyActiveAntiretroviralTherapy)ErasCrum,NancyFMD,MPH*†;Riffenburgh,RobertHPhD‡;Wegner,ScottMD†§;Agan,BrianKMD†∥;Tasker,SybilAMD†¶;Spooner,KatherineMMD†#;Armstrong,AdamWDO†**;Fraser,SusanMD††;Wallace,MarkRMD*†onBehalfoftheTriserviceAIDSClinicalConsortiumJAIDSJournalofAcquiredImmuneDeficiencySyndromes:February1st,2006-Volume41-Issue2-p194-200doi:10.1097/01.qai.0000179459.31562.16EpidemiologyandSocialScienceMethods:Comparisonsofdeath-relatedvariablesduringthe3eraswereperformed.Results:Thenumberofdeathsdeclinedoverthestudyperiod,with987deathsinthepre-HAARTera,159deathsintheearlyHAARTera(1997-1999),and78deathsinthelateHAARTera(2000-2003)(P<0.01).Theannualdeathratepeakedin1995(10.3per100patients)andthendeclinedto<2deathsper100personsinthelateHAARTera(P<0.01).Theproportionofdeathsattributabletoinfectiondecreased,butinfectionremainedtheleadingcauseofdeathinourcohort,followedbycancer.Ofthosewhodied,therewasanincreasingproportionofnon-HIV-relateddeaths(32%vs.9%;P<0.01),includingcardiacdisease(22%vs.8%;P<0.01)andtrauma(8%vs.2%;P=0.01)inthepost-HAARTversuspre-HAARTera.DespitetheabsenceofintravenousdruguseandthelowprevalenceofhepatitisCcoinfectioninourcohort,anincreasingproportionofdeathsintheHAARTerawereattributabletoliverdisease,althoughthenumbersaresmall.
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„Medicalerror—thethirdleadingcauseofdeathintheUS“,BritishMedicalJournal(3.5.2016).MartinMakaryfromJohnsHopkinsUniversitySchoolofMedicineinBaltimore.
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PERSPECTIVE
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Inmedicalhistorydecisionmakingwaspaternalistic.Replacedbypatientautonomy.Thisshiftisexemplifiedinthelegalrequirementofinformedconsenttotreatment.Shareddecisionmakingisnowtheideal.But:Thepatientistheultimativeandauthoritativedecisionmaker,becauseheorshealonedetermineswhatwillbedonetohisorherbodyandhowthisactionwillaffecthisorherlife.
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Chemical Substances (Medications) can lead to Mutations !
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HAARTdrivesEvolutionofHLA/HIV=Humangenes!
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ChristlMeyer,AIDSResearch,Vienna/Austria,2018
AIDS.2012Jul17;26(11):F21-9.doi:10.1097/QAD.0b013e328355fe8f.Abacavirinducesloadingofnovelself-peptidesintoHLA-B*57:01:an
autoimmunemodelforHLA-associateddrughypersensitivity.NorcrossMA,LuoS,LuL,BoyneMT,GomarteliM,RennelsAD,WoodcockJ,
MarguliesDH,McMurtreyC,VernonS,HildebrandWH,BuchliR.
SourceLaboratoryofImmunology,DivisionofTherapeuticProteins,Officeof
BiotechnologyProducts,CenterforDrugEvaluationandResearch,FoodandDrugAdministration,Bethesda,MD20892,[email protected]
CONCLUSION:Ourresultssupportamodelofdrug-inducedautoimmunityinwhichabacaviraltersthequantityandqualityofself-peptideloadingintoHLA-B57:01.Drug-inducedloadingofnovelself-peptidesintoHLA,
possiblybyabacavireitheralteringthebindingcleftormodifyingthepeptide-loadingcomplex,generatesanarrayofneo-antigenpeptidesthatdrivepolyclonalT-cellautoimmuneresponsesandmultiorgan
systemictoxicity.
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ChemImmunolAllergy.2012;97:18-31.doi:10.1159/000335613.Epub2012May3.Geneticsandthepotentialforpredictivetestsinadversedrugreactions.
PirmohamedM.TheWolfsonCentreforPersonalisedMedicine,DepartmentofMolecularandClinicalPharmacology,UniversityofLiverpool,Liverpool,[email protected]
Drughypersensitivityreactionsareanimmune-mediatedreactiontootherwiseinnocuousantigensderivedfromdrugs.Thesereactionscanaffectmanydifferentorgans,withtheskinbeingthecommonest.Skininvolvementcanrangeinseveritywithhypersensitivitysyndrome(orDRESS)andtheblisteringreactions(Stevens-Johnsonsyndrome,toxicepidermalnecrolysis),alsotermedseriouscutaneousadversedrug
reactions,beingthemostsevereandmostfeared.Thereisincreasingevidencefortheroleoftheimmunesysteminthepathogenesisofthesereactions,withdrug-specificTcellshavingbeenidentifiedinmany
patients.......HLAgenesasgenomicbiomarkersofpredisposition.The'revolution'startedwithabacavirwherethepredispositionto
hypersensitivitywaslinkedtoHLA-B*57:01,whichwasconfirmedinaclinicaltrial,andwhereitsimplementationhasshowntoreducetheincidenceofhypersensitivityinacost-effectivemanner.Sincethen,associationshavealsobeenshownforallopurinol(HLA-B*58:01)-andcarbamazepine(HLA-B*1502andHLA-A*3101)-inducedseriouscutaneousadversedrugreactions.ThelatterisinterestingsincetheassociationwithHLA-B*1502ispresentin
certainSouth-EasternAsianpopulations,andthepredispositionisphenotypespecific(onlyforSJS/TEN).TheutilityofthisbiomarkerhasbeenshowninaprospectivecohortstudyperformedinTaiwan.Bycontrast,theassociationwithHLA-A*3101isseeninmorediverseethnicgroups,andpredisposestomildaswellmoresevere
cutaneousreactionsassociatedwithcarbamazepine.ItisimportanttonotethatstrongHLAassociationshavealsobeenshownwithanumberofdrugsthatcauseliverinjuryincludingflucloxacillin,lumiracoxib,lapatinibandximelagatran,indicatingthattheimmunesystemisalsoimportantinthepathogenesisof
otherformsofdrug-inducedorgantoxicity.Copyright©2012S.KargerAG,Basel.
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Paracelsus:Everythingisdependentontheconcentration
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T1 T2
cellproliferation,antibodyproduction,lackofapoptosisT-celldecline
Immunebalance
Stress
?cancer „AIDS“
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Soul
Mind Body
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Asymbioticinteractionthatoriginatesfromthegenesoftheimmunesystemleadstocommunicationparticles(exo-andendosomes)thatactdifferentlywithintheimmunesystem.
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The whole cell-communication in and between cells of an organism depends on the activity of molecules like RNAs, Proteins, Exo- and Endosomes, Informosomes and Clathrines, to mention just some of them. The Journal of Immunology, 2005, 174: 4779–4788. HIV Type 1 Can Act as an APC upon Acquisition from theHost Cell of Peptide-Loaded HLA-DR and CD86 Molecules1 Jocelyn Roy, Genevie`ve Martin, Jean-Franc¸ois Gigue`re, Dave Be´langer, Myriam Pe´trin,and Michel J. Tremblay2
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TheHumanMicrobiomeProject(HMiP)triestospecifythegenesofthemicrobeslivingonandinourbodies.Wehave10-foldmoremicrobesthanwehavecellsinahumanbeing.
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Evolutionisacceleratedby(ancient)lateral(horizontal)genetransferfrommicrobestotheirhosts.
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Humansunderwentanevolutionaryadaptionprocesswhichwasinfluencedbygeography.Thisresultedindifferencesincludingtheimmunesystem.PeopleofAfricandescentshowreducedneutrophilcountduetoaregulatoryvariant.ThereisalsoanextensivegeneticdiversityintheHLAclassIIregionofAfricansfromGambiaandMalawi.ThisdiversityistwiceasextensiveasfoundinnorthernEuropeans.InconsequencewefinddifferencesinhumoralresponsesbetweenEthiopianandSwedishpersonswhoareclaimedtobe“infected”byHIV.
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Doxiadisetal.stateaphylogeneticevidencethatsupportsthenotionofthegenerationofnewHLA-DRBgenesasadynamicandsteadilyongoingprocess.Thisisduetothepresenceofindels(insertions/deletions),mainlymappingtointron.
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THEHIVGENOME„...analysisoftheproteinsofthevirusdemandsmassproductionandpurification...
Irepeat,wedidnotpurify.“LUCMontagnier,PasteurInstitute,July18th1997
From:EleniPapadopulosEleopulosBiophysicist,DepartmentofMedicalPhysics,RoyalPerthHospital,Perth,WesternAustralia
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Phylogenetictreeof„HIV“
P.M.SharpandB.H.Hahn/ColdSpringHarbPerspectMed2011;1:a006841www.perspectivesinmedicine.org 61ChristlMeyer,AIDSResearch,Vienna/
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Conclusion:HIVmeansevolutionaryadaptedgeneticvariationinsteadofvirusmutation!
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„OpenReadingFrames“Leadingtovariations
HIV-model
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HumanGenomeNature409,860-921(15February2001)/doi:10.1038/35057062;Received7December2000;Accepted9January2001
InitialsequencingandanalysisofthehumangenomeInternationbalHumanGenomeSequencingConsortiumEricS.Lander......Herewereporttheresultsofacollaborationinvolving20groupsfromtheUnitedStates,theUnitedKingdom,Japan,France,GermanyandChinatoproduceadraftsequenceofthehumangenome....Hundredsofhumangenesappearlikelytohaveresultedfromhorizontaltransferfrombacteriaatsomepointinthevertebratelineage....Dozensofgenesappeartohavebeenderivedfromtransposableelements....largerecentsegmentalduplications...muchmorefrequentinhumans...
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„HIV“isfoundmostneargenesandCGsequences/bacterialorigin;
Zaninietal.eLife2015;4:e11282.DOI:10.7554/eLife.11282https://www.sciencedirect.com/science/article/pii/S0092867402008644
PopulationgenomicsofintrapatientHIV-1
evolution
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MHCofthevertebrateimmunesystem:• Non-randomdistribution• IncreasedgenedensityintheMHC/HLA
Crisp,Aetal.Expressionofmultiplehorizontallyacquiredgenesisahallmarkofbothvertebrateandinvertebrategenomes.GenomeBiology;12March2015
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TranscriptionalanalysisforhostfactorsrequiredbyHIV-1wasperformedbyRNAinterference.Morethan250HIV-dependencyfactorswereidentified.Theseproteinsparticipateincellularfunctions.Transcriptionalanalysisrevealedthatthesegeneswereenrichedforhighexpressioninimmunecells.
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Jeremiasetal.claimthathumansemenisbothaninducerofananti-inflammatoryTH2immuneresponseandaninhibitorofTH1cellmediatedimmunity.Why?Thisprotectsthemalegenesinthefetus.
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HIVisanaturalproductinspermswhichhasitsoriginintheHLAandprotectsthefetusfrommaternalrejectionofpaternalantigensbyshiftingT1toT2.HeterosexualtransmissionofHIVisonlysuggestedwithadditionalpathogensinSTDs.Homosexualtransmissionisduetorejectionofalloantigens.Allogeneicimmunityprotectsfrominfectionbutcanberelatedtoallergiesalsointheoffspring.ThusHIVpositivitymeansanallergicreaction!
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MultipleinteractionsincellcommunicationareprovedconcerningHIV,specificallyinGALT(gutassociatedlymphoidtissue)whichmakessenseforprotectingthebodyfromstrangeinvadersfromnutrition!
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retrotransposon-mediateddiversity. https://openi.nlm.nih.gov/detailedresult.php?img=PMC2913931_1752-0509-4-96-1&req=4
Figure1:HIV-Humanproteininteractionnetwork.19HIVproteinsthatinteractwith1452humanproteinsthrough3959interactions.BluenodesarehumanproteinsandrednodesareHIVproteins.
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Gp120isactiveasasuperantigenthatincreasesTh2relatedantibodyproductionininfectionsasa“booster”andmightbeduetoallergyandautoimmunity.Stressisinvolvedingeneexpression.„HIV“canbeprotectivetocancer.MedicationsandHAARTmighthavedifferent(negative)impactsonthebalanceoftheTh1/Th2-system.
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The whole cell-communication in and between cells of an organism depends on the activity of molecules like RNAs, Proteins, Exo- and Endosomes, Informosomes and Clathrines, to mention just some of them. The Journal of Immunology, 2005, 174: 4779–4788. HIV Type 1 Can Act as an APC upon Acquisition from theHost Cell of Peptide-Loaded HLA-DR and CD86 Molecules1 Jocelyn Roy, Genevie`ve Martin, Jean-Franc¸ois Gigue`re, Dave Be´langer, Myriam Pe´trin,and Michel J. Tremblay2
ChristlMeyer,AIDSResearch,Vienna/Austria,2018
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TheRNA-family
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Source:CDC.EstimatedHIVincidenceamongadultsandadolescentsintheUnitedStates,2007–2010.HIVSurveillanceSupplementalReport2012;17(4)http://www.cdc.gov/hiv/topics/surveillance/resources/reports/index.htm#supplemental.Subpopulationsrepresenting2%orlessoftheoverallUSepidemicarenotreflectedinthischart.Abbreviations:MSM,menwhohavesexwithmen;IDU,injectiondruguser.
AfricanAmericansaccountedforanestimated44%ofallnewHIVinfectionsamongadultsandadolescents(aged13yearsorolder)in2010,despiterepresentingonly12%to14%oftheUSpopulation.
AfricanAmericansaretheracial/ethnicgroupmostaffectedbyHIV.
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“RPD[rapiddiseaseprogression]wasthreetimesmorelikelytooccurininfantsbornto[AZT]treatedmothers-comparedwith
findingsinuntreatedmothers.”deSouzaRSetal.EffectofprenatalzidovudineondiseaseprogressioninperinatallyHIV-1-
infectedinfants.JAcquirImmuneDeficSyndr.2000Jun1;24(2):154-161
"CombivirisclassifiedbytheFDAasapregnancycategoryCdrug.PregnancycategoryCmeansthatanimalstudieshaveshownanadverseeffectonthefetusandtherearenoadequateandwell-controlledstudiesinhumans"http://www.aidsmeds.com/archive/Combivir_1083.shtml
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The nervous and the immune system share a lot of biochemical molecules, i. e. Hormons (Cortisol) Transmitter (Gamma-Amino-Butyrat) Interleukine Il 2, Il 10...) Both systems are involved in learning processes! The Immune-System comprises high variability and fluctuation through Transposable Elements. It has to distinguish between SELF and NON-SELF! Learning means to add NEW informations to knowledge!
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Anergy
Anergy is the missing reaction to an antigen by shuting down the immune reaction. Anergy is a mechanism by which the immune system prevents T-cells from attacking the bodies own tissues. Anergy is a permanent characteristic. Under normal conditions it is not reactivated. Some systems are activated despite anergy by Interleukin-2. Problems: puberty and infectious tissues (lung cells with virus-infection).
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ALLOANTIGENs An allergic reaction against variants of molecules (glyco-proteins, nucleic acids) of the same species might occur if the variants of contact (blood-components, leucocytes, sperms) activate the immune-system. Those people might also test „HIV-positive“
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The Nobel Prize in Physiology or Medicine 2011 Bruce A. Beutler and Jules A. Hoffmann: Discoveries concerning the Activation of Innate Immunity Steinman : Discovery of the Dendritic Cell and its Role in Adaptive Immunity: Mediating the Communication between innate and adaptive immunity.
Toll-like receptor ligands will directly alter the functions of regulatory T cells
DendriticCells
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HIV- antibodies are • Autoantibodies as we all produce them. • Allergy-antibodies, which are induced by molecular similarity. • A hint for an active or • Imbalanced immune-system (stress). • Increased after some vaccinations.
HIV – „Viruses“ are • Particels of cell-communication (Endo- and Exosomes).
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The Rest belongs to other diseases or wrong diagosis! Like hunger, malaria, tuberculosis, lung- and gut-infections, drugs.
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AIDS is gene expression and / or self-organized mutation (genome extension) and therefore EVOLUTION under elevated stress.
The aim is the survival under unfavorable environmental conditions. Medications themselves bring on these situations by which the cell responds with mutations.
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1. Genetics,HIVandtheImmuneSystem2. Epigenetics3. MicrobesinEvolution4. Immunization5. WhatdoesitmeantobeHuman?
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Epigenetics Stimuli from the environnement change gene expression. This effect can be transmitted through generations.
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Psychoneuroimmunology Psychoneuroimmunology (PNI) is an interdisciplinary field of research, which deals with the interaction of the nerve system, the hormone system and the immune system. The scientific basis is that messenger molecules (like hormones and other substances) of the nervous system influence the immune system and vice verse.
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Pregnancy and the future of the next generations:
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InstituteofScienceinSocietyReport30/09/15
OrganicFoodduringMother'sPregnancyReducesRiskofMaleBirthDefects
ExpectingmotherseatingmostlyorganicproducereduceriskofurogenitalanomaliesinmaleoffspringDrEvaSirinathsinghji
Pesticidesaretheotherobviouscandidatefortheobserveddisparityindisease
ratesbetweenthoseeatingorganicversusconventionalfoods.Severalclassesofpesticidehavebeenshowntohaveendocrinedisruptingeffectsincludingglyphosate,2,4-D,atrazine,endosulfan,linurin,vinclozolinanddichlorodiphenyldichloroethylene(DDE).
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Syncytin-mediatedcell–cellfusion
DupressoirAetal.PNAS2005;102:725-730
©2005byNationalAcademyofSciences
Syncytin and placenta development
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Syncytin, whichisexpressedbyendogenousretrovirusesofthepregnantwomen,leadstocell-fusionbybuildinguptheplacentainnormaldevelopment.
DupressoirAetal.PNAS2005;102:725-730
Humans have 400% more of retroviral genes than of human genes
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Why it is so important that mothers breastfeed their babies:
• The antibodies of the mother protect the child from infections. • The emotional relationship and the primal sense of trust are strengthened.
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EVOLUTION and MUTATION
Extinction of the Population
Extiction of the Individual
„genechaos“Lackofgenetic
diversity
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Result: The more of Stress The more of Mutations.
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Prenatalstressaltersthebraintranscriptomeinmalenewbornoffspring.
ZucchiFCR,YaoY,WardID,IlnytskyyY,etal.(2013)MaternalStressInducesEpigeneticSignaturesofPsychiatricandNeurologicalDiseasesintheOffspring.PLoSONE8(2):e56967.doi:10.1371/journal.pone.0056967http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056967
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Normalcellularhomeostasisisadelicatebalancebetweentherateandmagnitudeofoxidantformationandtherateofoxidantelimination.Oxidativestresscan,therefore,bedefinedasthepathogenicoutcomeoftheoverproductionofoxidantsthatoverwhelmsthecellularantioxidantcapacity. 96ChristlMeyer,AIDSResearch,Vienna/
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