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dc.contributor.authorAsmal, Mohammed
dc.contributor.authorWhitney, James B.
dc.contributor.authorLuedemann, Corinne
dc.contributor.authorCarville, Angela
dc.contributor.authorSteen, Robert G.
dc.contributor.authorLetvin, Norman L.
dc.contributor.authorGeiben-Lynn, Ralf
dc.date.accessioned2013-04-24T17:28:07Z
dc.date.issued2012
dc.identifier.citationAsmal, Mohammed, James B. Whitney, Corinne Luedemann, Angela Carville, Robert G. Steen, Norman L. Letvin, and Ralf Geiben-Lynn. 2012. In vivo anti-HIV activity of the heparin-activated serine protease inhibitor antithrombin III encapsulated in lymph-targeting immunoliposomes. PLoS ONE 7(11): e48234.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10581393
dc.description.abstractEndogenous serine protease inhibitors (serpins) are anti-inflammatory mediators with multiple biologic functions. Several serpins have been reported to modulate HIV pathogenesis, or exhibit potent anti-HIV activity in vitro, but the efficacy of serpins as therapeutic agents for HIV in vivo has not yet been demonstrated. In the present study, we show that heparin-activated antithrombin III (hep-ATIII), a member of the serpin family, significantly inhibits lentiviral replication in a non-human primate model. We further demonstrate greater than one log10 reduction in plasma viremia in the nonhuman primate system by loading of hep-ATIII into anti-HLA-DR immunoliposomes, which target tissue reservoirs of viral replication. We also demonstrate the utility of hep-ATIIII as a potential salvage agent for HIV strains resistant to standard anti-retroviral treatment. Finally, we applied gene-expression arrays to analyze hep-ATIII-induced host cell interactomes and found that downstream of hep-ATIII, two independent gene networks were modulated by host factors prostaglandin synthetase-2, ERK1/2 and NFκB. Ultimately, understanding how serpins, such as hep-ATIII, regulate host responses during HIV infection may reveal new avenues for therapeutic intervention.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0048234en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487854/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectImmunologyen_US
dc.subjectImmunityen_US
dc.subjectImmune Defenseen_US
dc.subjectImmunoregulationen_US
dc.subjectImmunotherapyen_US
dc.subjectInflammationen_US
dc.subjectInnate Immunityen_US
dc.subjectImmune Responseen_US
dc.subjectImmunomodulationen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMacaqueen_US
dc.subjectMedicineen_US
dc.subjectInfectious Diseasesen_US
dc.subjectViral Diseasesen_US
dc.subjectHIVen_US
dc.subjectRetrovirology and HIV immunopathogenesisen_US
dc.titleIn Vivo Anti-HIV Activity of the Heparin-Activated Serine Protease Inhibitor Antithrombin III Encapsulated in Lymph-Targeting Immunoliposomesen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorAsmal, Mohammed
dc.date.available2013-04-24T17:28:07Z
dc.identifier.doi10.1371/journal.pone.0048234*
dash.contributor.affiliatedAsmal, Mohammed
dash.contributor.affiliatedWhitney, James
dash.contributor.affiliatedSteen, Robert


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