{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T18:28:40Z","timestamp":1783362520708,"version":"3.54.6"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The Toll-like receptor (TLR) 7 is a viral sensor for detecting single-stranded ribonucleic acid (ssRNA), the activation of which can induce intracellular innate immunity against viral infections. Imiquimod, a synthetic ligand for TLR7, has been successfully used for the topical treatment of genital\/perianal warts in immunocompetent individuals. We studied the effect of imiquimod on the human immunodeficiency virus (HIV) infection of primary human macrophages and demonstrated that the treatment of cells with imiquimod effectively inhibited infection with multiple strains (Bal, YU2, and Jago) of HIV. This anti-HIV activity of imiquimod was the most potent when macrophages were treated prior to infection. Infection of macrophages with pseudotyped HIV NL4-3-\u0394Env-eGFP-Bal showed that imiquimod could block the viral entry. Further mechanistic studies revealed that while imiquimod had little effect on the interferons (IFNs) expression, its treatment of macrophages resulted in the increased production of the CC chemokines (human macrophage inflammatory protein-1 alpha (MIP-1\u03b1), MIP-1\u03b2, and upon activation regulated normal T cells expressed and secreted (RANTES)), the natural ligands of HIV entry co-receptor CCR5, and decreased the expression of CD4 and CCR5. The addition of the antibodies against the CC chemokines to macrophage cultures could block imiquimod-mediated HIV inhibition. These findings provide experimental evidence to support the notion that TLR7 participates in the intracellular immunity against HIV in macrophages, suggesting the further clinical evaluation of imiquimod for its additional benefit of treating genital\/perianal warts in people infected with HIV.<\/jats:p>","DOI":"10.3390\/biology10070661","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors"],"prefix":"10.3390","volume":"10","author":[{"given":"Feng-Zhen","family":"Meng","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Wuhan University, Wuhan 430000, China"},{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Biao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-6721","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1439-455X","authenticated-orcid":false,"given":"Wei","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Wuhan University, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Zhe","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114316","DOI":"10.1016\/j.bcp.2020.114316","article-title":"Detection of Viral Infections by Innate Immunity","volume":"183","author":"Carty","year":"2021","journal-title":"Biochem. 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