{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:43:08Z","timestamp":1790624588786,"version":"4.1.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Current advances in combined antiretroviral therapy have rendered HIV infection a chronic, manageable disease; however, the problem of persistent immune activation still remains despite treatment. The immune cell receptor SLAMF7 has been shown to be upregulated in diseases characterized by chronic immune activation. In this study, we studied the function of the SLAMF7 receptor in immune cells of HIV patients and the impacts of SLAMF7 signaling on peripheral immune activation. We observed increased frequencies of SLAMF7+ PBMCs in HIV+ individuals in a clinical phenotype-dependent manner, with discordant and long-term nonprogressor patients showing elevated SLAMF7 levels, and elite controllers showing levels comparable to healthy controls. We also noted that SLAMF7 was sensitive to IFN-\u237a stimulation, a factor elevated during HIV infection. Further studies revealed SLAMF7 to be a potent inhibitor of the monocyte-derived proinflammatory chemokine CXCL10 (IP-10) and other CXCR3 ligands, except in a subset of HIV+ patients termed SLAMF7 silent (SF7S). Studies utilizing small molecule inhibitors revealed that the mechanism of CXCL10 inhibition is independent of known SLAMF7 binding partners. Furthermore, we determined that SLAMF7 activation on monocytes is able to decrease their susceptibility to HIV-1 infection in vitro via downregulation of CCR5 and upregulation of the CCL3L1 chemokine. Finally, we discovered that neutrophils do not express SLAMF7, are CXCL10+ at baseline, are able to secrete CXCL10 in response to IFN-\u237a and LPS, and are nonresponsive to SLAMF7 signaling. These findings implicate the SLAMF7 receptor as an important regulator of IFN-\u237a\u2013driven innate immune responses during HIV infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1800847","type":"journal-article","created":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T01:15:52Z","timestamp":1544490952000},"page":"228-238","source":"Crossref","is-referenced-by-count":40,"title":["SLAMF7 Is a Critical Negative Regulator of IFN-\u03b1\u2013Mediated CXCL10 Production in Chronic HIV Infection"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-4754","authenticated-orcid":false,"given":"Patrick","family":"O\u2019Connell","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8205-3613","authenticated-orcid":false,"given":"Yuliya","family":"Pepelyayeva","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja K","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-3795","authenticated-orcid":false,"given":"Sean","family":"Hyslop","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B","family":"Crawford","sequence":"additional","affiliation":[{"name":"Center for Integrative Toxicology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane","family":"Pereira-Hicks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Godbehere","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-6227","authenticated-orcid":false,"given":"Linda","family":"Dale","sequence":"additional","affiliation":[{"name":"Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-5428","authenticated-orcid":false,"given":"Peter","family":"Gulick","sequence":"additional","affiliation":[{"name":"Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2144-428X","authenticated-orcid":false,"given":"Norbert E","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Center for Integrative Toxicology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"},{"name":"Department of Pharmacology and Toxicology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-1420","authenticated-orcid":false,"given":"Andrea","family":"Amalfitano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"},{"name":"Department of Pediatrics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A","family":"Aldhamen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"},{"name":"College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"2025030417555910300_r1","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1016\/S0140-6736(13)60104-X","article-title":"Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs","volume":"381","author":"Katlama","year":"2013","journal-title":"Lancet"},{"key":"2025030417555910300_r2","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.bjid.2012.11.007","article-title":"Aging with HIV: a practical review","volume":"17","author":"Cardoso","year":"2013","journal-title":"Braz. 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