{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:20:37Z","timestamp":1792189237921,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T00:00:00Z","timestamp":1421625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions.<\/jats:p>","DOI":"10.3390\/toxins7010156","type":"journal-article","created":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T10:53:54Z","timestamp":1421664834000},"page":"156-169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Recombinant Maize Ribosome-Inactivating Protein Transiently Reduces Viral Load in SHIV89.6 Infected Chinese Rhesus Macaques"],"prefix":"10.3390","volume":"7","author":[{"given":"Rui-Rui","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-Yee","family":"Au","sequence":"additional","affiliation":[{"name":"Center for Protein Science and Crystallography, School of Life Sciences, the Chinese University of Hong Kong, Shatin N.T. 999077, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Min","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS and STI Control, Yuxi Centers for Disease Control and Prevention, Yuxi 653100, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3853-517X","authenticated-orcid":false,"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Hua","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Law","sequence":"additional","affiliation":[{"name":"Center for Protein Science and Crystallography, School of Life Sciences, the Chinese University of Hong Kong, Shatin N.T. 999077, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Mak","sequence":"additional","affiliation":[{"name":"Center for Protein Science and Crystallography, School of Life Sciences, the Chinese University of Hong Kong, Shatin N.T. 999077, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kam-Bo","family":"Wong","sequence":"additional","affiliation":[{"name":"Center for Protein Science and Crystallography, School of Life Sciences, the Chinese University of Hong Kong, Shatin N.T. 999077, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Pang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pang-Chui","family":"Shaw","sequence":"additional","affiliation":[{"name":"Center for Protein Science and Crystallography, School of Life Sciences, the Chinese University of Hong Kong, Shatin N.T. 999077, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-0324","authenticated-orcid":false,"given":"Yong-Tang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.toxicon.2013.02.005","article-title":"Ribosome-inactivating proteins: From toxins to useful proteins","volume":"67","author":"Stirpe","year":"2013","journal-title":"Toxicon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.drudis.2012.03.007","article-title":"Ribosome-inactivating proteins: Current status and biomedical applications","volume":"17","author":"Puri","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12250-011-3223-8","article-title":"Ribosome inactivating proteins from plants inhibiting viruses","volume":"26","author":"Kaur","year":"2011","journal-title":"Virol. Sin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/0306-3623(92)90131-3","article-title":"Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor and anti-AIDS activities from Cucurbitaceae plants","volume":"23","author":"Ng","year":"1992","journal-title":"Gen. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0014-4827(92)90353-A","article-title":"High sensitivity of cultured human trophoblasts to ribosome-inactivating proteins","volume":"201","author":"Battelli","year":"1992","journal-title":"Exp. Cell. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1006\/bbrc.1999.0922","article-title":"Pokeweed antiviral protein isoforms PAP-I, PAP-II, and PAP-III depurinate RNA of human immunodeficiency virus (HIV)-1","volume":"260","author":"Rajamohan","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0014-5793(00)01389-2","article-title":"The plant ribosome inactivating proteins luffin and saporin are potent inhibitors of HIV-1 integrase","volume":"471","author":"Au","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1007\/s11033-009-9668-2","article-title":"Trichosanthin inhibits integration of human immunodeficiency virus type 1 through depurinating the long-terminal repeats","volume":"37","author":"Zhao","year":"2010","journal-title":"Mol. Biol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12208","DOI":"10.1073\/pnas.91.25.12208","article-title":"Human immunodeficiency virus type 1(HIV-1) inhibition, DNA-binding, RNA-binding, and ribosome inactivation activities in the N-terminal segments of the plant anti-HIV protein GAP31","volume":"91","author":"Kung","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0092-8674(00)81529-9","article-title":"Solution structure of anti-HIV-1 and anti-tumor protein MAP30: Structural insights into its multiple functions","volume":"99","author":"Wang","year":"1999","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0378-1119(95)00186-A","article-title":"Anti-HIV and anti-tumor activities of recombinant MAP30 from bitter melon","volume":"161","author":"Huang","year":"1995","journal-title":"Gene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.bbrc.2009.11.060","article-title":"A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase-structural and modeling insight into its functions","volume":"391","author":"Li","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1128\/AAC.38.2.260","article-title":"Safety, activity, and pharmacokinetics of GLQ223 in patients with AIDS and AIDS-related complex","volume":"38","author":"Kahn","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0022-3565(24)35240-1","article-title":"Toxicity, biological activity, and pharmacokinetics of TXU (anti-CD7)-pokeweed antiviral protein in chimpanzees and adult patients infected with human immunodeficiency virus","volume":"291","author":"Uckun","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0014-5793(02)03182-4","article-title":"Transport of protein toxins into cells: Pathways used by ricin, cholera toxin and shiga toxin","volume":"529","author":"Sandvig","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2165\/00139709-200322010-00007","article-title":"Ricin poisoning","volume":"22","author":"Bradberry","year":"2003","journal-title":"Toxicol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1093\/nar\/gkm687","article-title":"Structure-function study of maize ribosome-inactivating protein: Implications for the internal inactivation region and the sole glutamate in the active site","volume":"35","author":"Mak","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.1093\/nar\/gkq551","article-title":"A switch-on mechanism to activate maize ribosome-inactivating protein for targeting HIV-infected cells","volume":"38","author":"Law","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1399-3089.2009.00554.x","article-title":"Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta)","volume":"16","author":"Chen","year":"2009","journal-title":"Xenotransplantation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1073\/pnas.86.8.2844","article-title":"GLQ223: An inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage","volume":"86","author":"McGrath","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1006\/bbrc.1999.1213","article-title":"Proteolytic fragments of anti-HIV and anti-tumor proteins MAP30 and GAP31 are biologically active","volume":"262","author":"Huang","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1126\/science.1139247","article-title":"Evolutionary and biomedical insights from the rhesus macaque genome","volume":"316","author":"Gibbs","year":"2007","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/17130","article-title":"Origin of HIV-1 in the chimpanzee pan troglodytes troglodytes","volume":"397","author":"Gao","year":"1999","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1126\/science.1126531","article-title":"Chimpanzee reservoirs of pandemic and nonpandemic HIV-1","volume":"313","author":"Keele","year":"2006","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1128\/jvi.70.6.3617-3627.1996","article-title":"Genetic characterization of new west african simian immunodeficiency virus SIVsm: Geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop","volume":"70","author":"Chen","year":"1996","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1126\/science.3159089","article-title":"Isolation of T-cell tropic HTLV-III-like retrovirus from macaques","volume":"228","author":"Daniel","year":"1985","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.2412295","article-title":"Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus HTLV-III","volume":"230","author":"Letvin","year":"1985","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/cmi.2009.55","article-title":"The influence of age and sex on the cell counts of peripheral blood leukocyte subpopulations in Chinese rhesus macaques","volume":"6","author":"Xia","year":"2009","journal-title":"Cell. Mol. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1128\/jvi.70.5.3198-3206.1996","article-title":"An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian\/human immunodeficiency virus in rhesus monkeys","volume":"70","author":"Reimann","year":"1996","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1126\/science.272.5265.1167","article-title":"Prognosis in HIV-1 infection predicted by the quantity of virus in plasma","volume":"272","author":"Mellors","year":"1996","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1001\/jama.1995.03530070052029","article-title":"Natural history of HIV-1 cell-free viremia","volume":"274","author":"Henrard","year":"1995","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1001\/jama.1996.03540020027025","article-title":"Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study","volume":"276","author":"Blattner","year":"1996","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1056\/NEJM199602153340703","article-title":"Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS","volume":"334","author":"Hartigan","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1126\/science.272.5265.1124","article-title":"Viral counts count in HIV infection","volume":"272","author":"Ho","year":"1996","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/JVI.75.2.589-594.2001","article-title":"Human immunodeficiency virus type 1 protease cleavage site mutations associated with protease inhibitor cross-resistance selected by indinavir, ritonavir, and\/or saquinavir","volume":"75","author":"Cote","year":"2001","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6836","DOI":"10.1128\/JVI.76.13.6836-6840.2002","article-title":"A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance","volume":"76","author":"Harrigan","year":"2002","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1128\/CMR.15.2.247-277.2002","article-title":"Genotypic testing for human immunodeficiency virus type 1 drug resistance","volume":"15","author":"Shafer","year":"2002","journal-title":"Clin. Microbiol. Rev."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/1\/156\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:41:47Z","timestamp":1760215307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/1\/156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,19]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,1]]}},"alternative-id":["toxins7010156"],"URL":"https:\/\/doi.org\/10.3390\/toxins7010156","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,19]]}}}