{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:01:45Z","timestamp":1791144105357,"version":"4.1.0"},"reference-count":91,"publisher":"American Society for Microbiology","issue":"22","license":[{"start":{"date-parts":[[2014,11,15]],"date-time":"2014-11-15T00:00:00Z","timestamp":1416009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We investigated the hypothesis that the correlation between the class I HLA types of an individual and whether that individual spontaneously controls HIV-1 is mediated by the targeting of specific epitopes by CD8\n            <jats:sup>+<\/jats:sup>\n            T cells. By measuring gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay responses to a panel of 257 optimally defined epitopes in 341 untreated HIV-infected persons, including persons who spontaneously control viremia, we found that the correlation between HLA types and control is mediated by the targeting of specific epitopes. Moreover, we performed a graphical model-based analysis that suggested that the targeting of specific epitopes is a cause of such control\u2014that is, some epitopes are protective rather than merely associated with control\u2014and identified eight epitopes that are significantly protective. In addition, we use an\n            <jats:italic>in silico<\/jats:italic>\n            analysis to identify protein regions where mutations are likely to affect the stability of a protein, and we found that the protective epitopes identified by the ELISPOT analysis correspond almost perfectly to such regions. This\n            <jats:italic>in silico<\/jats:italic>\n            analysis thus suggests a possible mechanism for control and could be used to identify protective epitopes that are not often targeted in natural infection but that may be potentially useful in a vaccine. Our analyses thus argue for the inclusion (and exclusion) of specific epitopes in an HIV vaccine.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Some individuals naturally control HIV replication in the absence of antiretroviral therapy, and this ability to control is strongly correlated with the HLA class I alleles that they express. Here, in a large-scale experimental study, we provide evidence that this correlation is mediated largely by the targeting of specific CD8\n            <jats:sup>+<\/jats:sup>\n            T-cell epitopes, and we identify eight epitopes that are likely to cause control. In addition, we provide an\n            <jats:italic>in silico<\/jats:italic>\n            analysis indicating that control occurs because mutations within these epitopes change the stability of the protein structures. This\n            <jats:italic>in silico<\/jats:italic>\n            analysis also identified additional epitopes that are not typically targeted in natural infection but may lead to control when included in a vaccine, provided that other epitopes that would otherwise distract the immune system from targeting them are excluded from the vaccine.\n          <\/jats:p>","DOI":"10.1128\/jvi.01004-14","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T01:28:45Z","timestamp":1409189325000},"page":"12937-12948","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":73,"title":["HIV Control Is Mediated in Part by CD8\n            <sup>+<\/sup>\n            T-Cell Targeting of Specific Epitopes"],"prefix":"10.1128","volume":"88","author":[{"given":"Florencia","family":"Pereyra","sequence":"first","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, 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