Regulation of HIV-Gag Expression and Targeting to the Endolysosomal/Secretory Pathway by the Luminal Domain of Lysosomal-Associated Membrane Protein (LAMP-1) Enhance Gag-Specific Immune Response

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author GODINHO, Rodrigo Maciel da Costa
MATASSOLI, Flavio Lemos
LUCAS, Carolina Goncalves de Oliveira
RIGATO, Paula Ordonhez FMUSP-HC
GONCALVES, Jorge Luiz Santos
SATO, Maria Notomi FMUSP-HC
MACIEL JR., Milton
PECANHA, Ligia Maria Torres
AUGUST, J. Thomas
MARQUES JR., Ernesto Torres de Azevedo
ARRUDA, Luciana Barros de
dc.date.issued 2014
dc.identifier.citation PLOS ONE, v.9, n.6, article ID e99887, 11p, 2014
dc.identifier.issn 1932-6203
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/7471
dc.description.abstract We have previously demonstrated that a DNA vaccine encoding HIV-p55gag in association with the lysosomal associated membrane protein-1 (LAMP-1) elicited a greater Gag-specific immune response, in comparison to a DNA encoding the native gag. In vitro studies have also demonstrated that LAMP/Gag was highly expressed and was present in MHCII containing compartments in transfected cells. In this study, the mechanisms involved in these processes and the relative contributions of the increased expression and altered traffic for the enhanced immune response were addressed. Cells transfected with plasmid DNA constructs containing p55gag attached to truncated sequences of LAMP-1 showed that the increased expression of gag mRNA required p55gag in frame with at least 741 bp of the LAMP-1 luminal domain. LAMP luminal domain also showed to be essential for Gag traffic through lysosomes and, in this case, the whole sequence was required. Further analysis of the trafficking pathway of the intact LAMP/Gag chimera demonstrated that it was secreted, at least in part, associated with exosome-like vesicles. Immunization of mice with LAMP/gag chimeric plasmids demonstrated that high expression level alone can induce a substantial transient antibody response, but targeting of the antigen to the endolysosomal/secretory pathways was required for establishment of cellular and memory response. The intact LAMP/gag construct induced polyfunctional CD4(+) T cell response, which presence at the time of immunization was required for CD8(+) T cell priming. LAMP-mediated targeting to endolysosomal/secretory pathway is an important new mechanistic element in LAMP-mediated enhanced immunity with applications to the development of novel anti-HIV vaccines and to general vaccinology field.
dc.description.sponsorship · National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [R37-AI41908, R21-AI44317]
· Brazilian Ministry of Health
· CAPES
· CNPq
· FAPERJ
· FINEP
dc.language.iso eng
dc.publisher PUBLIC LIBRARY SCIENCE
dc.relation.ispartof Plos One
dc.rights openAccess
dc.subject.other t-cell responses; virus type-1 gag; class-ii compartment; mhc class-i; dna vaccination; lymphocyte responses; antigen presentation; codon usage; neutralizing antibodies; longitudinal analysis
dc.title Regulation of HIV-Gag Expression and Targeting to the Endolysosomal/Secretory Pathway by the Luminal Domain of Lysosomal-Associated Membrane Protein (LAMP-1) Enhance Gag-Specific Immune Response
dc.type article
dc.rights.holder Copyright PUBLIC LIBRARY SCIENCE
dc.description.group LIM/56
dc.identifier.doi 10.1371/journal.pone.0099887
dc.identifier.pmid 24932692
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author RIGATO, Paula Ordonhez:FM:
hcfmusp.author SATO, Maria Notomi:FM:MDT
hcfmusp.author.external · GODINHO, Rodrigo Maciel da Costa:Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Virol, Rio De Janeiro, Brazil
· MATASSOLI, Flavio Lemos:Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Virol, Rio De Janeiro, Brazil
· LUCAS, Carolina Goncalves de Oliveira:Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Virol, Rio De Janeiro, Brazil
· GONCALVES, Jorge Luiz Santos:Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Imunol, Rio De Janeiro, Brazil
· MACIEL JR., Milton:Naval Med Res Ctr, Infect Dis Directorate, Enter Dis Dept, Silver Spring, MD USA; Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA
· PECANHA, Ligia Maria Torres:Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Imunol, Rio De Janeiro, Brazil
· AUGUST, J. Thomas:Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA
· MARQUES JR., Ernesto Torres de Azevedo:Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA; Ctr Vaccine Res, Dept Infect Dis & Microbiol, Pittsburgh, PA USA; Fiocruz Pernambuco, Dept Virol, Recife, PE, Brazil
· ARRUDA, Luciana Barros de:Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Dept Virol, Rio De Janeiro, Brazil
hcfmusp.origem.id 2-s2.0-84903136057
hcfmusp.origem.id WOS:000337738600077
hcfmusp.publisher.city SAN FRANCISCO
hcfmusp.publisher.country USA
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dc.description.index MEDLINE
hcfmusp.citation.scopus 8
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Estados Unidos
hcfmusp.scopus.lastupdate 2021-07-13


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