{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T15:15:05Z","timestamp":1772723705246,"version":"3.50.1"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30 AI 082151"],"award-info":[{"award-number":["P30 AI 082151"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH113425"],"award-info":[{"award-number":["R01MH113425"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD8+ T cells do not rely solely on cytotoxic functions for significant HIV control. Moreover, the noncytotoxic CD8+ T cell antiviral response is a primary mediator of natural HIV control such as that seen in HIV elite controllers and long-term nonprogressors that does not require combined antiretroviral therapy. In this study, we investigated the biological factors contributing to the noncytotoxic control of HIV replication mediated by primary human CD8+ T cells. We report that canonical Wnt signaling inhibits HIV transcription in an MHC-independent, noncytotoxic manner and that mediators of this pathway correlate with HIV controller clinical status. We show that CD8+ T cells express all 19 Wnts and CD8+ T cell\u2013conditioned medium (CM) induced canonical Wnt signaling in infected recipient cells while simultaneously inhibiting HIV transcription. Antagonizing canonical Wnt activity in CD8+ T cell CM resulted in increased HIV transcription in infected cells. Further, Wnt2b expression was upregulated in HIV controllers versus viremic patients, and in vitro depletion of Wnt2b and\/or Wnt9b from CD8+ CM reversed HIV inhibitory activity. Finally, plasma concentration of Dkk-1, an antagonist of canonical Wnt signaling, was higher in viremic patients with lower CD4 counts. This study demonstrates that canonical Wnt signaling inhibits HIV and significantly correlates with HIV controller status.<\/jats:p>","DOI":"10.4049\/jimmunol.1801379","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T19:50:12Z","timestamp":1599249012000},"page":"2046-2055","source":"Crossref","is-referenced-by-count":19,"title":["Canonical Wnts Mediate CD8+ T Cell Noncytolytic Anti\u2013HIV-1 Activity and Correlate with HIV-1 Clinical Status"],"prefix":"10.1093","volume":"205","author":[{"given":"Jennillee","family":"Wallace","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogens and Immunity, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas D","family":"Narasipura","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly E","family":"Sha","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey L","family":"French","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Rush University Medical Center , Chicago, IL 60612"},{"name":"Stroger Hospital of Cook County, Cook County Health and Hospitals System , Chicago, IL 60612"},{"name":"Ruth M. Rothstein CORE Center, Cook County Health and Hospitals System , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-3904","authenticated-orcid":false,"given":"Lena","family":"Al-Harthi","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity, Rush University Medical Center , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"2025030417505245300_r1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/COH.0b013e328344f35e","article-title":"Epidemiology and clinical characteristics of elite controllers","volume":"6","author":"Okulicz","year":"2011","journal-title":"Curr. Opin. 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