{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:09:20Z","timestamp":1791288560730,"version":"4.3.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2000,5,1]],"date-time":"2000-05-01T00:00:00Z","timestamp":957139200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2000,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human immunodeficiency virus type 1 (HIV-1) produces two polyproteins, Pr55\n            <jats:sup>Gag<\/jats:sup>\n            and Pr160\n            <jats:sup>Gag-Pol<\/jats:sup>\n            , that are cleaved into mature functional subunits by the virally encoded protease. Drugs that inhibit this protease are an important part of anti-HIV therapy. We studied the ordered accumulation of Gag and Gag-Pol processing intermediates by variably blocking the protease with HIV-1 protease inhibitors (PIs). Variable protease inhibition caused accumulation of a complex pattern of processing intermediates, which was the same after incubating HIV-1-infected cells with increasing concentrations of either one of the peptidomimetic inhibitors indinavir, saquinavir (SQV), ritonavir (RTV), nelfinavir, and SC-52151 or one of the nonpeptidomimetic inhibitors DMP450, DMP323, PNU-140135, and PNU-109112 for 3 days. The patterns of Gag and Gag-Pol processing intermediate accumulation were nearly identical when the following were compared: cell- versus virion-associated proteins, HIV-1-infected transformed cell lines versus primary human peripheral blood mononuclear cells (PBMCs) and HIV-1\n            <jats:sub>MN<\/jats:sub>\n            versus HIV-1\n            <jats:sub>IIIB<\/jats:sub>\n            virus strains. RTV was a more potent inhibitor of p24 production in PBMCs than SQV by approximately 7-fold, whereas SQV was a more potent inhibitor in transformed cells than RTV by approximately 30-fold. Although the antiretroviral potency of HIV-1 PIs may change as a function of cell type, the polyprotein intermediates that accumulate with increasing drug concentrations are the same. These results support sequential processing of Gag and Gag-Pol polyproteins by the HIV-1 protease and may have important implications for understanding common cross-resistance pathways.\n          <\/jats:p>","DOI":"10.1128\/aac.44.5.1397-1403.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"1397-1403","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Comparison of Human Immunodeficiency Virus Type 1 Pr55\n            <sup>Gag<\/sup>\n            and Pr160\n            <sup>Gag-Pol<\/sup>\n            Processing Intermediates That Accumulate in Primary and Transformed Cells Treated with Peptidic and Nonpeptidic Protease Inhibitors"],"prefix":"10.1128","volume":"44","author":[{"given":"R. Renae","family":"Speck","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Pharmacology and Molecular Sciences1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Flexner","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Pharmacology and Molecular Sciences1 and"},{"name":"<!--label omitted: 2-->Medicine,2 The Johns Hopkins University School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Juan","family":"Tian","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Molecular Microbiology and Immunology, The Johns Hopkins University School of Hygiene and Public Health,3 Baltimore, Maryland 21287-5554"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fang","family":"Yu","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Molecular Microbiology and Immunology, The Johns Hopkins University School of Hygiene and Public Health,3 Baltimore, Maryland 21287-5554"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.2775"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.10.2229"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.11.2367"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/374569a0"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0166-3542(91)90045-S","article-title":"Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase.","volume":"16","author":"Craig J. 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