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dc.contributor.authorRodriguez, William Richard
dc.contributor.authorAddo, Marylyn Martina
dc.contributor.authorRathod, Almas
dc.contributor.authorFitzpatrick, Cecily A
dc.contributor.authorYu, Xu
dc.contributor.authorPerkins, Beth
dc.contributor.authorRosenberg, Eric Scott
dc.contributor.authorAltfeld, Marcus
dc.contributor.authorWalker, Bruce David
dc.date.accessioned2011-05-10T01:45:09Z
dc.date.issued2004
dc.identifier.citationRodriguez, William R., Marylyn M. Addo, Almas Rathod, Cecily A. Fitzpatrick, Xu G. Yu, Beth Perkins, Eric S. Rosenberg, Marcus Altfeld, and Bruce D. Walker. 2004. CD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjects. Journal of Translational Medicine 2: 15.en_US
dc.identifier.issn1479-5876en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4885971
dc.description.abstractBackground: CD8+ T cell responses are known to be important to the control of HIV-1 infection. While responses to reverse transcriptase and most structural and accessory proteins have been extensively studied, CD8 T cell responses specifically directed to the HIV-1 enzymes Protease and Integrase have not been well characterized, and few epitopes have been described in detail. Methods: We assessed comprehensively the CD8 T cell responses to synthetic peptides spanning Protease and Integrase in 56 HIV-1 infected subjects with acute, chronic, or controlled infection using IFN-γ-Elispot assays and intracellular cytokine staining. Fine-characterization of novel CTL epitopes was performed on peptide-specific CTL lines in Elispot and \(^{51}\)Chromium-release assays. Results: Thirteen (23%) and 38 (68%) of the 56 subjects had detectable responses to Protease and Integrase, respectively, and together these targeted most regions within both proteins. Sequence variability analysis confirmed that responses cluster largely around conserved regions of Integrase, but responses against a large, highly conserved region of the N-terminal DNA-binding domain of Integrase were not readily detected. CD8 T cell responses targeted regions of Protease that contain known Protease inhibitor mutation residues, but strong Protease-specific CD8 T cell responses were rare. Fine-mapping of targeted epitopes allowed the identification of three novel, HLA class I-restricted, frequently-targeted optimal epitopes. There were no significant correlations between CD8 T cell responses to Protease and Integrase and clinical disease category in the study subjects, nor was there a correlation with viral load. Conclusions: These findings confirm that CD8 T cell responses directed against HIV-1 include potentially important functional regions of Protease and Integrase, and that pharmacologic targeting of these enzymes will place them under both drug and immune selection pressure.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1479-5876-2-15en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC441415/pdf/en_US
dash.licenseLAA
dc.titleCD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjectsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Translational Medicineen_US
dash.depositing.authorRodriguez, William Richard
dc.date.available2011-05-10T01:45:09Z
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherSPH^Immunology and Infectious Diseasesen_US
dc.identifier.doi10.1186/1479-5876-2-15*
dash.contributor.affiliatedRodriguez, William Richard
dash.contributor.affiliatedYu, Xu
dash.contributor.affiliatedAddo, Marylyn Martina
dash.contributor.affiliatedAltfeld, Marcus
dash.contributor.affiliatedRosenberg, Eric
dash.contributor.affiliatedWalker, Bruce
dc.identifier.orcid0000-0001-6122-9245


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