{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:39:52Z","timestamp":1791095992731,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"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":[[2002,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HIV-1 infection impairs a number of macrophage effector functions, thereby contributing to development of opportunistic infections and the pathogenesis of AIDS. Fc\u03b3R-mediated phagocytosis by human monocyte-derived macrophages (MDM) is inhibited by HIV-1 infection in vitro, and the underlying mechanism was investigated in this study. Inhibition of phagocytosis directly correlated with the multiplicity of HIV-1 infection. Expression of surface Fc\u03b3Rs was unaffected by HIV-1 infection, suggesting that inhibition of phagocytosis occurred during or after receptor binding. HIV-1 infection of MDM markedly inhibited tyrosine phosphorylation of the cellular proteins, which occurs following engagement of Fc\u03b3Rs, suggesting a defect downstream of initial receptor activation. Fc\u03b3R-mediated phagocytosis in HIV-infected MDM was associated with inhibition of phosphorylation of tyrosine kinases from two different families, Hck and Syk, defective formation of Syk complexes with other tyrosine-phosphorylated proteins, and inhibition of paxillin activation. Down-modulation of protein expression but not mRNA of the \u03b3 signaling subunit of Fc\u03b3R (a docking site for Syk) was observed in HIV-infected MDM. Infection of MDM with a construct of HIV-1 in which nef was replaced with the gene for the \u03b3 signaling subunit augmented Fc\u03b3R-mediated phagocytosis, suggesting that down-modulation of \u03b3-chain protein expression in HIV-infected MDM caused the defective Fc\u03b3R-mediated signaling and impairment of phagocytosis. This study is the first to demonstrate a specific alteration in phagocytosis signal transduction pathway, which provides a mechanism for the observed impaired Fc\u03b3R-mediated phagocytosis in HIV-infected macrophages and contributes to the understanding of how HIV-1 impairs cell-mediated immunity leading to HIV-1 disease progression.<\/jats:p>","DOI":"10.4049\/jimmunol.168.6.2895","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T00:31:13Z","timestamp":1398040273000},"page":"2895-2903","source":"Crossref","is-referenced-by-count":63,"title":["HIV-1 Down-Modulates \u03b3 Signaling Chain of Fc\u03b3R in Human Macrophages: A Possible Mechanism for Inhibition of Phagocytosis"],"prefix":"10.1093","volume":"168","author":[{"given":"Katherine","family":"Kedzierska","sequence":"first","affiliation":[{"name":"AIDS Pathogenesis Research Unit, Macfarlane Burnet Center, University of Melbourne , Melbourne ,","place":["Australia"]},{"name":"Departments of Medicine and Biochemistry, Monash University, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Ellery","sequence":"additional","affiliation":[{"name":"AIDS Pathogenesis Research Unit, Macfarlane Burnet Center, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson","family":"Mak","sequence":"additional","affiliation":[{"name":"AIDS Pathogenesis Research Unit, Macfarlane Burnet Center, University of Melbourne , Melbourne ,","place":["Australia"]},{"name":"Biochemistry, Monash University, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon R","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M","family":"Crowe","sequence":"additional","affiliation":[{"name":"AIDS Pathogenesis Research Unit, Macfarlane Burnet Center, University of Melbourne , Melbourne ,","place":["Australia"]},{"name":"National Center for HIV Virology Research, University of Melbourne , Melbourne ,","place":["Australia"]},{"name":"Departments of Medicine and Biochemistry, Monash University, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Jaworowski","sequence":"additional","affiliation":[{"name":"AIDS Pathogenesis Research Unit, Macfarlane Burnet Center, University of Melbourne , Melbourne ,","place":["Australia"]},{"name":"National Center for HIV Virology Research, University of Melbourne , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,3,15]]},"reference":[{"key":"2025032712351718100_R1","first-page":"13","volume-title":"Clin. 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