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The HIV-1 matrix protein p17 does cross the blood-brain barrier

2022Journal article Restricted access
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dc.contributor.authorCaccuri, Francesca
dc.contributor.authorNeves, Vera
dc.contributor.authorGano, Lurdes
dc.contributor.authorCorreia, João D. G.
dc.contributor.authorOliveira, Maria-Cristina
dc.contributor.authorMazzuca, Pietro
dc.contributor.authorCaruso, Arnaldo
dc.contributor.authorCastanho, Miguel A. R. B.
dc.date.accessioned2023-05-23T10:31:27Z
dc.date.available2023-05-23T10:31:27Z
dc.date.issued2022
dc.description© 2022 American Society for Microbiology. All Rights Reserved.pt_PT
dc.description.abstractHuman immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation in HIV-1-infected (HIV) patients. Furthermore, detection of the HIV-1 matrix protein p17 (p17) in the central nervous system (CNS) and its ability to form toxic assemblies in the brain have been recently confirmed. Here, we show for the first time, using both an in vitro blood-brain barrier (BBB) model and in vivo biodistribution studies in healthy mice, that p17 can cross the BBB. There is rapid brain uptake with 0.35%  0.19% of injected activity per gram of tissue (IA/g) 2 min after administration, followed by brain accumulation with 0.28%  0.09% IA/g after 1 h. The interaction of p17 with chemokine receptor 2 (CXCR2) at the surface of brain endothelial cells triggers transcytosis. The present study supports the hypothesis of a direct role of free p17 in neuronal dysfunction in HAND by demonstrating its intrinsic ability to reach the CNS.pt_PT
dc.description.sponsorshipThis study was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC) grant 20108 (to A.C.) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 828774 (to M.C.)pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJournal of Virology, January 2022, Volume 96, Issue 1 e01200-21pt_PT
dc.identifier.doi10.1128/JVI.01200-21pt_PT
dc.identifier.eissn1098-5514
dc.identifier.issn0022-538X
dc.identifier.urihttp://hdl.handle.net/10451/57519
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Microbiologypt_PT
dc.relation''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
dc.relation.publisherversionhttps://journals.asm.org/journal/jvipt_PT
dc.subjectHIV-1 matrix protein p17pt_PT
dc.subjectHIV-associated neurocognitive disorderpt_PT
dc.subjectBloodbrain barrierpt_PT
dc.subjectTranscytosispt_PT
dc.subjectin vivo biodistributionpt_PT
dc.titleThe HIV-1 matrix protein p17 does cross the blood-brain barrierpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitle''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/828774/EU
oaire.citation.issue1pt_PT
oaire.citation.titleJournal of Virologypt_PT
oaire.citation.volume96pt_PT
oaire.fundingStreamH2020
person.familyNameNeves
person.familyNameBarrela Patricio Gano
person.familyNameCorreia
person.familyNamedas Neves Oliveira
person.familyNameCastanho
person.givenNameVera
person.givenNameMaria Lurdes
person.givenNameJoão
person.givenNameMaria Cristina
person.givenNameMiguel
person.identifier953259
person.identifierJ-6929-2013
person.identifier1064683
person.identifier.ciencia-id671C-1860-A160
person.identifier.ciencia-idC11F-51E3-6084
person.identifier.ciencia-idEC11-F3E9-78A2
person.identifier.ciencia-idE21A-316D-935F
person.identifier.orcid0000-0002-2989-7208
person.identifier.orcid0000-0001-7186-2060
person.identifier.orcid0000-0002-7847-4906
person.identifier.orcid0000-0002-5708-3885
person.identifier.orcid0000-0001-7891-7562
person.identifier.ridO-2176-2018
person.identifier.ridJ-7036-2013
person.identifier.scopus-author-id26537945300
person.identifier.scopus-author-id8976995900
person.identifier.scopus-author-id7202364104
person.identifier.scopus-author-id56605575600
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication032ea886-49b5-40c6-bb5f-5cb7db74efaf
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