{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:15:31Z","timestamp":1776932131125,"version":"3.51.2"},"reference-count":54,"publisher":"Proceedings of the National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,10,13]]},"abstract":"<jats:p>Infection with HIV-1 results in pronounced immune suppression and susceptibility to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As we have shown for<jats:italic>Mycobacterium avium<\/jats:italic>complex (MAC) and<jats:italic>Pneumocystis carinii<\/jats:italic>, macrophages infected with opportunistic pathogens and within lymphoid tissues containing OI, exhibit striking levels of viral replication. To explore potential underlying mechanisms for increased HIV-1 replication associated with coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and their levels of tumor necrosis factor \u03b1 (TNF\u03b1) and HIV-1 coreceptors monitored. MAC enhanced TNF\u03b1 production<jats:italic>in vitro<\/jats:italic>, consistent with its expression in coinfected lymph nodes. Using a polyclonal antibody to the CCR5 coreceptor that mediates viral entry of macrophage tropic HIV-1, a subset of unstimulated monocytes was shown to be CCR5-positive by fluorescence-activated cell sorter analysis. After stimulation with MAg or infection with MAC, CCR5 expression was increased at both the mRNA level and on the cell surface. Up-regulation of CCR5 by MAC was not paralleled by an increase in the T cell tropic coreceptor, CXCR4. Increases in NF-\u03baB, TNF\u03b1, and CCR5 were consistent with the enhanced production of HIV-1 in MAg-treated adherent macrophage cultures as measured by HIV-1 p24 levels. Increased CCR5 was also detected in coinfected lymph nodes as compared with tissues with only HIV-1. The increased production of TNF\u03b1, together with elevated expression of CCR5, provide potential mechanisms for enhanced infection and replication of HIV-1 by macrophages in OI-infected cells and tissues. Consequently, treating OI may inhibit not only the OI-induced pathology, but also limit the viral burden.<\/jats:p>","DOI":"10.1073\/pnas.95.21.12574","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:40:11Z","timestamp":1027694411000},"page":"12574-12579","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["<i>Mycobacterium avium<\/i>complex augments macrophage HIV-1 production and increases CCR5 expression"],"prefix":"10.1073","volume":"95","author":[{"given":"S. M.","family":"Wahl","sequence":"first","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]},{"given":"T.","family":"Greenwell-Wild","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]},{"given":"G.","family":"Peng","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]},{"given":"H.","family":"Hale-Donze","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]},{"given":"T. M.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]},{"given":"D.","family":"Mizel","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]},{"given":"J. M.","family":"Orenstein","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental Research, 30 Convent Drive, MSC 4352, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Department of Pathology, George Washington University, Washington, DC 20037"}]}],"member":"341","published-online":{"date-parts":[[1998,10,13]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1086\/517297"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91110-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.4049\/jimmunol.157.3.1271","volume":"157","author":"Goletti D","year":"1996","unstructured":"D Goletti, D Weissman, R W Jackson, N M H Graham, D Vlahov, R S Klein, S S Munsiff, L Ortona, R Cauda, A S Fauci J Immunol 157, 1271\u20131278 (1996).","journal-title":"J Immunol"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.1.7812542"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.62.1.67"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.2.401"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1994.tb06582.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5320.1857"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-0191-0_15"},{"key":"e_1_3_3_10_2","first-page":"89","volume":"151","author":"Frankel S S","year":"1997","unstructured":"S S Frankel, K Tennar-Racz, P Racz, B M Wenig, C H Hansen, D Heffner, A M Nelson, M Pope, R M Steinman Am J Pathol 151, 89\u201396 (1997).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.115"},{"key":"e_1_3_3_12_2","first-page":"593","volume":"148","author":"Mosialos G","year":"1996","unstructured":"G Mosialos, M Birkenbach, S Ayehunie, F Matsumura, G S Pinkus, E Kieff, E Langhoff Am J Pathol 148, 593\u2013600 (1996).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5270.1955"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/381661a0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/381667a0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/163.1.78"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/384529a0"},{"key":"e_1_3_3_18_2","unstructured":"Peng G. Hale-Donze H. Wild T. Orenstein J. M. & Wahl S. M. (1998) 5th Conference on Retrovirus and Opportunistic Infections February 1\u20135 1998 Chicago IL p. 86."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(84)90251-X"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.4049\/jimmunol.139.4.1342","volume":"139","author":"Wahl S M","year":"1987","unstructured":"S M Wahl, N McCartney-Francis, D A Hunt, P D Smith, L M Wahl, I M Katona J Immunol 139, 1342\u20131347 (1987).","journal-title":"J Immunol"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1904628"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118056"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.3.1141.1141_1141_1149"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","first-page":"4822","DOI":"10.4049\/jimmunol.158.10.4822","volume":"158","author":"Doherty T M","year":"1997","unstructured":"T M Doherty, A Sher J Immunol 158, 4822\u20134831 (1997).","journal-title":"J Immunol"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(85)90442-7"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/8.2.113"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.12.3587"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","first-page":"6226","DOI":"10.4049\/jimmunol.159.12.6226","volume":"159","author":"Dickensheets H L","year":"1997","unstructured":"H L Dickensheets, R P Donnelly J Immunol 159, 6226\u201333 (1997).","journal-title":"J Immunol"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(97)90079-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.5.969"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"985","DOI":"10.4049\/jimmunol.160.2.985","volume":"160","author":"Guignard F","year":"1998","unstructured":"F Guignard, C Combadiere, H L Tiffany, P M Murphy J Immunol 160, 985\u2013992 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.7.2336"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)06231-9"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.4.1645"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb07141.x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.4049\/jimmunol.159.8.4109","volume":"159","author":"Toossi Z","year":"1997","unstructured":"Z Toossi, B D Hamilton, M H Phillips, L E Averill, J J Ellner, A Salvekar J Immunol 159, 4109\u20134116 (1997).","journal-title":"J Immunol"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81313-6"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81314-8"},{"key":"e_1_3_3_39_2","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.4049\/jimmunol.159.6.2824","volume":"159","author":"Garrait V","year":"1997","unstructured":"V Garrait, J Cadranel, H Esvant, I Herry, P Morinet, C Mayaud, D Israel-Biet J Immunol 159, 2824\u20132830 (1997).","journal-title":"J Immunol"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.9.7080-7082.1997"},{"key":"e_1_3_3_41_2","first-page":"S4","volume":"23","author":"Chu T","year":"1994","unstructured":"T Chu, R Jaffe Br J Cancer Suppl 23, S4\u2013S10 (1994).","journal-title":"Br J Cancer Suppl"},{"key":"e_1_3_3_42_2","first-page":"543","volume":"150","author":"Pinkus G S","year":"1997","unstructured":"G S Pinkus, J L Pinkus, E Langhoff, F Matsumura, S Yamashiro, G Mosialos, J W Said Am J Pathol 150, 543\u2013562 (1997).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/360258a0"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.6.2433"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-218"},{"key":"e_1_3_3_46_2","first-page":"573","volume":"170","author":"Horsburgh C R","year":"1994","unstructured":"C R Horsburgh, B Metchock, S M Gordon, J A Havlik, J E McGowan, S E Thompson N Engl J Med 170, 573\u2013577 (1994).","journal-title":"N Engl J Med"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91817-6"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.3.1082.1082"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.6.1727"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605093341903"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.6.1191"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)02190-9"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/387183a0"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/387188a0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.21.12574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T12:23:10Z","timestamp":1682166190000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.21.12574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,10,13]]},"references-count":54,"journal-issue":{"issue":"21","published-print":{"date-parts":[[1998,10,13]]}},"alternative-id":["10.1073\/pnas.95.21.12574"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.21.12574","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,10,13]]},"assertion":[{"value":"1998-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}