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Here we demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and potent<jats:italic>S<\/jats:italic>-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in monocytes and macrophages. MGBG is selectively concentrated by these cells through a mechanism consistent with active transport by the polyamine transporter. Using a macrophage-tropic reporter virus tagged with the enhanced green fluorescent protein, we demonstrate that MGBG decreases the frequency of HIV-infected cells. The effect is dose dependent and correlates with the production of HIV p24 in culture supernatants. This anti-HIV effect was further confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA in both monocytes and macrophages.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Our work demonstrates for the first time the selective concentration of MGBG by monocytes\/macrophages, leading to the inhibition of HIV-1 expression and a reduction in proviral load within macrophage cultures. These results suggest that MGBG may be useful in adjunctive macrophage-targeted therapy for HIV infection.<\/jats:p>","DOI":"10.1128\/jvi.01692-15","type":"journal-article","created":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T02:55:30Z","timestamp":1438224930000},"page":"11176-11189","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone"],"prefix":"10.1128","volume":"89","author":[{"given":"Xia","family":"Jin","sequence":"first","affiliation":[{"name":"Pathologica LLC, Burlingame, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"McGrath","sequence":"additional","affiliation":[{"name":"UCSF Department of Laboratory Medicine, Medicine, and Pathology; AIDS &amp; Cancer Specimen Resource, San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Pathologica LLC, Burlingame, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-7-32"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.59.062806.123001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165706"},{"key":"e_1_3_3_5_2","first-page":"1","article-title":"Significant reduction in HIV-1 plasma viral load but not in proviral infected cells during sub-optimal antiretroviral therapy","volume":"14","author":"Riva E","year":"2000","unstructured":"Riva E, Antonelli G, Solmone MC, Turriziani O, Narciso P, Tozzi V, Dianzani F. 2000. 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