Highly Differentiated, Resting Gn-Specific Memory CD8(+) T Cells Persist Years after Infection by Andes Hantavirus

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dc.contributor.authorManigold, Tobias
dc.contributor.authorMori, Andres
dc.contributor.authorGraumann, Rebecca
dc.contributor.authorLlop, Elena
dc.contributor.authorSimon, Valeska
dc.contributor.authorFerres, Marcela
dc.contributor.authorValdivieso, Francisca
dc.contributor.authorCastillo, Constanza
dc.contributor.authorHjelle, Brian
dc.contributor.authorVial, Pablo
dc.date.accessioned2024-01-10T12:39:23Z
dc.date.available2024-01-10T12:39:23Z
dc.date.issued2010
dc.description.abstractIn man, infection with South American Andes virus (ANDV) causes hantavirus cardiopulmonary syndrome (HCPS). HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-gamma ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3(+)CD8(+) T cells were specific for the single HLA-B*3501-restricted epitope Gn(465-473) years after the acute infection. Remarkably, Gn(465-473)-specific cells readily secreted IFN-gamma, granzyme B and TNF-alpha but not IL-2 upon stimulation and showed a 'revertant' CD45RA(+)CD27(-)CD28(-)CCR7(-)CD127(-) effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T cells are critical for viral control and protective immunity. If so, Gn-derived immunodominant epitopes could be of high value for future ANDV vaccines.
dc.description.funderFONDECYT
dc.description.funderUDD
dc.description.funderNIH
dc.description.funderConvenio de Desempeno UTA/MECESUP-2
dc.description.funderNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
dc.fechaingreso.objetodigital2024-05-09
dc.format.extent16 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1371/journal.ppat.1000779
dc.identifier.eissn1553-7374
dc.identifier.issn1553-7366
dc.identifier.pubmedidMEDLINE:20174562
dc.identifier.urihttps://doi.org/10.1371/journal.ppat.1000779
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77184
dc.identifier.wosidWOS:000275295900029
dc.information.autorucMedicina;Ferres M;S/I;66180
dc.issue.numero2
dc.language.isoen
dc.nota.accesoSin adjunto
dc.publisherPUBLIC LIBRARY SCIENCE
dc.revistaPLOS PATHOGENS
dc.rightsregistro bibliográfico
dc.subjectNEUTRALIZING ANTIBODY-RESPONSE
dc.subjectVIRUS NUCLEOCAPSID PROTEIN
dc.subjectHANTAAN VIRUS
dc.subjectPULMONARY-SYNDROME
dc.subjectHEMORRHAGIC-FEVER
dc.subjectRENAL SYNDROME
dc.subjectPERSON TRANSMISSION
dc.subjectIMMUNE-RESPONSES
dc.subjectACUTE-PHASE
dc.subjectEPITOPES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHighly Differentiated, Resting Gn-Specific Memory CD8(+) T Cells Persist Years after Infection by Andes Hantavirus
dc.typeartículo
dc.volumen6
sipa.codpersvinculados66180
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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