?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F10248%2F&rft.title=RELATIONSHIP+BETWEEN+SYSTEMIC+AND+CENTRAL+NERVOUS+SYSTEM+MONOCYTE%2FMACROPHAGE+INFECTION+IN+SIMIAN+IMMUNODEFICIENCY+VIRUS+ENCEPHALITIS&rft.creator=Bissel%2C+Stephanie+Jane&rft.description=Approximately+%C2%BC+of+AIDS+patients+develop+HIVE%2C+the+pathologic+entity+associated+with+cognitive%2C+motor%2C+and+behavioral+deficits+attributed+to+synaptic+damage+and+neuronal+loss.+It+still+remains+unclear+why+only+a+subset+of+HIV-infected+individuals+develops+abundant+central+nervous+system+(CNS)+macrophage%2Fmicroglia+infection+that+characterizes+HIVE.+The+overarching+hypothesis+of+this+body+of+work+is+that+simian+immunodeficiency+virus+(SIV)+encephalitis+(SIVE)+is+the+CNS+manifestation+of+a+systemic+increase+in+SIV+infection+and+activation+of+monocyte%2Fmacrophage+elements.+Specifically%2C+we+examined+the+relationship+of+infected+and+activated+monocyte%2Fmacrophage+elements+outside+of+the+CNS+during+the+evolution+of+lentiviral+encephalitis+to+the+presence+of+infected+macrophages+in+the+CNS.+We+studied+three+models+of+SIV+infection%3A+SIV-infection+of+rhesus+and+pigtailed+macaques+and+SIV-infection+of+CD8%2B+T+cell+depleted+macaques.+Antibody-mediated+CD8%2B+T+cell+depletion+did+not+increase+the+incidence+of+SIVE+in+infected+rhesus+macaques.+In+SIV-infected+rhesus+macaques%2C+we+examined+whether+presence+of+activated+macrophages+or+SIV-infected+macrophages+is+associated+with+the+presence+of+neuronal+damage.+The+presence+of+abundant+infected+macrophages+in+the+CNS+is+related+to+postsynaptic+neuronal+damage+in+macaques+with+SIVE.+At+the+same+time+cerebrospinal+fluid+viral+load+increased+in+SIV-infected+CD8-depleted+rhesus+and+non-depleted+pigtailed+macaques+that+developed+encephalitis%2C+monocyte-derived+macrophages+produced+more+virus+ex+vivo+than+macaques+that+did+not+develop+encephalitis.+Compared+to+pigtailed+macaques+that+did+not+develop+SIVE%2C+the+monocyte+associated+SIV-DNA+load+of+monocytes+was+elevated+in+macaques+that+developed+SIVE.+Pigtailed+macaques+with+SIVE+had+more+infected+macrophages+in+peripheral+organs%2C+with+the+exception+of+lymph+nodes%2C+than+macaques+without+SIVE.+Longitudinal+analysis+of+phenotypic+markers+of+monocyte+activation+show+that+increases+in+proportion+of+CD14%2B%2FCD16%2B+monocytes+is+associated+with+chronic+disease.+Brains+with+SIVE+have+greater+numbers+of+T+cells+with+cytotoxic+potential.+In+conclusion%2C+these+findings+suggest+that+inherent+differences+in+host+macrophage+viral+production+or+immune+response+to+macrophage+infection+are+associated+with+development+of+encephalitis.+Further+understanding+of+the+differential+role+monocyte%2Fmacrophages+have+in+the+development+of+lentiviral+encephalitis+will+identify+therapeutic+targets+to+halt+this+public+health+epidemic.&rft.date=2006-02-03&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F10248%2F1%2Fbisselsj_etd2005-4.pdf&rft.identifier=++Bissel%2C+Stephanie+Jane++(2006)+RELATIONSHIP+BETWEEN+SYSTEMIC+AND+CENTRAL+NERVOUS+SYSTEM+MONOCYTE%2FMACROPHAGE+INFECTION+IN+SIMIAN+IMMUNODEFICIENCY+VIRUS+ENCEPHALITIS.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++