Medical Microbiology

RNAviruses 451

HumanImmuneDeficiencyVirus(HIV)

HIVreplication

HIVcaninfectT4lymphocytesandothercellsbearingtheCD4markerontheir

surface.TheCD4moleculeisthemainreceptorforHIV,ormorepreciselyfor

itsgp1 20 (Fig.8. 14 ).Inaddition,eitherthechemokinereceptorCCR5(macro-

phage-tropicR5HIVstrains)orCXCR4(Tcell-tropicX4strains)isusedasacore-

ceptor.Personswith(homozygotic)missingCCR5arehighlyresistanttoHIVinfec-

tion.Anumberofothercoreceptorsarealsoactivedependingontheviralstrain

involved.HIVisthentakeninbythecell.Afteruncoating,reversetranscriptiontakes

placeinthecytoplasm.Therestoftheviralreplicationprocessbasicallycorresponds

tothedescriptionofretroviralreplicationonp.385.Theinteractionofthemany

differentcontributingcontrolgenesisresponsibleforthelonglatencyperiodand

subsequentviralreplication(seealsoFig.8. 14 ).

ReplicationofHIVtakestheformofalyticcycle,i.e.,itresultsindestructionof

thehostcell,makingitanexceptionamongretroviruses.Itmustalsobenoted

thatthecelldestructionmechanismhasnotbeencompletelyexplained.Cellfusions

areinducedbyX4strains(syncytialformation).Theseprocessesoccurlateinthe

infectioncycleandareassociatedwithprogressiontoAIDS.R5strainsdonotinduce

syncytia,arepresentearlyinthecourseoftheinfection,andaremainlyresponsible

fortransmissionofHIV.Besidesvirus-inducedcelldestruction(p.392),apoptosis

alsoappearstoplayanimportantroleintheeliminationofCD4+cells.

Pathogenesisandclinicalpicture.AIDSwasdescribedasadiscretepathol-

ogyoftheimmunesystemin 1981 .Thepathogenicityofthediseaseisbased

onsuppressionofcellularimmunityasaresultofthelossoftheCD4+Thelper

cells.

Theprimaryinfectioneitherremainsinapparentormanifestsas“acute

retroviralsyndrome”withconjunctivitis,pharyngitis,exanthem,andlymph-

adenopathy,aswellasatransitorymeningoencephalitisinsomecases.p24

antigen(Fig.8. 14 )isdetectableinserumafterabout 14 days,i.e.,beforethe

antibodies.Thisstageisfollowedbyalongperiodofclinicallatency(thein-

cubationperiodisdescribedas 10 years),duringwhichthecarrierisclinically

normalbutmaybeinfectious.TheHIviruscanpersistinalatentstateinCD4+

Tlymphocytes,macrophages,andtheLangerhanscellsintheskin.Appar-

ently,viralreplicationcontinuesthroughoutthisperiod,especiallyinlym-

phoidorgans.

ThedropinCD4+lymphocytesandtheriseintheviruscount(viralload,

seebelow)inperipheralbloodisfollowedbythelymphadenopathicstage.

Opportunisticinfectionsthensetin,frequentlycombinedwithlymphomas,

theotherwiserareKaposisarcoma,orso-calledAIDSencephalopathy(sub-

acuteAIDSencephalitis,AIDSdementiacomplex).Similarneurologicalsymp-

tomsmayalsobeinducedbecauseofHIV-inducedimmunosuppression,

8

Kayser, Medical Microbiology © 2005 Thieme