{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:26:02Z","timestamp":1791296762980,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T00:00:00Z","timestamp":1269907200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0000642","type":"journal-article","created":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T21:39:47Z","timestamp":1269898787000},"page":"e642","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["Nelfinavir, an HIV-1 Protease Inhibitor, Induces Oxidative Stress\u2013Mediated, Caspase-Independent Apoptosis in Leishmania Amastigotes"],"prefix":"10.1371","volume":"4","author":[{"given":"Pranav","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lodge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Trudel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Ouellet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ouellette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel J.","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1128\/CMR.00061-07","article-title":"The relationship between leishmaniasis and AIDS: the second 10 years.","volume":"21","author":"J Alvar","year":"2008","journal-title":"Clin Microbiol Rev"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1550-7408.2000.tb00008.x","article-title":"<italic>Leishmania<\/italic>, <italic>Trypanosoma<\/italic> and monoxenous trypanosomatids as emerging opportunistic agents.","volume":"47","author":"JP Dedet","year":"2000","journal-title":"J Eukaryot Microbiol"},{"key":"ref3","first-page":"357","article-title":"<italic>Leishmania<\/italic>\/HIV co-infections in the second decade.","volume":"123","author":"I Cruz","year":"2006","journal-title":"Indian J Med Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.4049\/jimmunol.172.5.3086","article-title":"<italic>Leishmania infantum<\/italic> promotes replication of HIV type 1 in human lymphoid tissue cultured ex vivo by inducing secretion of the proinflammatory cytokines TNF-alpha and IL-1 alpha.","volume":"172","author":"C Zhao","year":"2004","journal-title":"J Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1099\/vir.0.81647-0","article-title":"In primary human monocyte-derived macrophages exposed to Human immunodeficiency virus type 1, does the increased intracellular growth of <italic>Leishmania infantum<\/italic> rely on its enhanced uptake?","volume":"87","author":"C Zhao","year":"2006","journal-title":"J Gen Virol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1001\/jama.1997.03540260059037","article-title":"HIV-1 protease inhibitors. A review for clinicians.","volume":"277","author":"SG Deeks","year":"1997","journal-title":"JAMA"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1086\/318708","article-title":"Influence of highly active antiretroviral therapy on the outcome of subclinical visceral leishmaniasis in human immunodeficiency virus-infected patients.","volume":"32","author":"R de la Rosa","year":"2001","journal-title":"Clin Infect Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1179\/000349803225002615","article-title":"The impact of highly active antiretroviral therapy (HAART) on visceral leishmaniasis in Spanish patients who are co-infected with HIV.","volume":"97","author":"R Lopez-Velez","year":"2003","journal-title":"Ann Trop Med Parasitol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/00002030-200106150-00017","article-title":"Declining incidence of visceral leishmaniasis in HIV-infected individuals in the era of highly active antiretroviral therapy.","volume":"15","author":"E Rosenthal","year":"2001","journal-title":"AIDS"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ijantimicag.2005.04.003","article-title":"Antileishmanial activity of HIV protease inhibitors.","volume":"26","author":"D Savoia","year":"2005","journal-title":"Int J Antimicrob Agents"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1086\/592280","article-title":"Intracellular survival of <italic>Leishmania<\/italic> species that cause visceral leishmaniasis is significantly reduced by HIV-1 protease inhibitors.","volume":"198","author":"N Trudel","year":"2008","journal-title":"J Infect Dis"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.1158\/1078-0432.CCR-07-0161","article-title":"Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis <italic>in vitro<\/italic> and <italic>in vivo<\/italic>.","volume":"13","author":"JJ Gills","year":"2007","journal-title":"Clin Cancer Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e4918","DOI":"10.1371\/journal.pone.0004918","article-title":"HIV aspartyl peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of <italic>Leishmania amazonensis<\/italic>.","volume":"4","author":"LO Santos","year":"2009","journal-title":"PLoS ONE"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1128\/IAI.70.7.3727-3735.2002","article-title":"Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in <italic>Leishmania amazonensis<\/italic> amastigotes.","volume":"70","author":"P Holzmuller","year":"2002","journal-title":"Infect Immun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/sj.cdd.4401071","article-title":"Cell death in <italic>Leishmania<\/italic> induced by stress and differentiation: programmed cell death or necrosis?","volume":"9","author":"H Zangger","year":"2002","journal-title":"Cell Death Differ"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/sj.cdd.4400952","article-title":"Programmed cell death in the unicellular protozoan parasite <italic>Leishmania<\/italic>.","volume":"9","author":"N Lee","year":"2002","journal-title":"Cell Death Differ"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/sj.cdd.4400951","article-title":"On the evolution of programmed cell death: apoptosis of the unicellular eukaryote <italic>Leishmania major<\/italic> involves cysteine proteinase activation and mitochondrion permeabilization.","volume":"9","author":"D Arnoult","year":"2002","journal-title":"Cell Death Differ"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1242\/jcs.114.13.2461","article-title":"Hydrogen peroxide induces apoptosis-like death in <italic>Leishmania donovani<\/italic> promastigotes.","volume":"114","author":"M Das","year":"2001","journal-title":"J Cell Sci"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/sj.cdd.4402002","article-title":"Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex.","volume":"14","author":"N Sen","year":"2007","journal-title":"Cell Death Differ"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1126\/science.1112680","article-title":"The genome of the kinetoplastid parasite, <italic>Leishmania major<\/italic>.","volume":"309","author":"AC Ivens","year":"2005","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1242\/jcs.014050","article-title":"Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites.","volume":"121","author":"S Gannavaram","year":"2008","journal-title":"J Cell Sci"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/cdd.2008.85","article-title":"The caspase-independent algorithm of programmed cell death in <italic>Leishmania<\/italic> induced by baicalein: the role of LdEndoG, LdFEN-1 and LdTatD as a DNA \u2018degradesome\u2019.","volume":"15","author":"S BoseDasgupta","year":"2008","journal-title":"Cell Death Differ"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.molbiopara.2008.09.007","article-title":"<italic>Leishmania infantum<\/italic> expresses a mitochondrial nuclease homologous to EndoG that migrates to the nucleus in response to an apoptotic stimulus.","volume":"163","author":"E Rico","year":"2009","journal-title":"Mol Biochem Parasitol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"6726","DOI":"10.1074\/jbc.M510382200","article-title":"Involvement of endonuclease G in nucleosomal DNA fragmentation under sustained endogenous oxidative stress.","volume":"281","author":"Y Ishihara","year":"2006","journal-title":"J Biol Chem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.exppara.2005.07.003","article-title":"Trypanosomatid protozoa: a simplified DNA isolation procedure.","volume":"111","author":"B Rotureau","year":"2005","journal-title":"Exp Parasitol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0014-5793(97)00669-8","article-title":"JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess delta psi changes in intact cells: implications for studies on mitochondrial functionality during apoptosis.","volume":"411","author":"S Salvioli","year":"1997","journal-title":"FEBS Lett"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0924-8579(03)00125-0","article-title":"Characterisation of <italic>Leishmania donovani<\/italic> promastigotes resistant to hexadecylphosphocholine (miltefosine).","volume":"22","author":"K Seifert","year":"2003","journal-title":"Int J Antimicrob Agents"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1128\/AAC.48.8.3010-3015.2004","article-title":"Possible mechanism of miltefosine-mediated death of <italic>Leishmania donovani<\/italic>.","volume":"48","author":"NK Verma","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1074\/mcp.M600319-MCP200","article-title":"A proteomics screen implicates HSP83 and a small kinetoplastid calpain-related protein in drug resistance in <italic>Leishmania donovani<\/italic> clinical field isolates by modulating drug-induced programmed cell death.","volume":"6","author":"B Vergnes","year":"2007","journal-title":"Mol Cell Proteomics"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1128\/AAC.42.12.3097","article-title":"Axenically grown amastigotes of <italic>Leishmania infantum<\/italic> used as an in vitro model to investigate the pentavalent antimony mode of action.","volume":"42","author":"D Sereno","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/35083620","article-title":"Endonuclease G is an apoptotic DNase when released from mitochondria.","volume":"412","author":"LY Li","year":"2001","journal-title":"Nature"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/sj.cdd.4400944","article-title":"Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation.","volume":"8","author":"G van Loo","year":"2001","journal-title":"Cell Death Differ"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1146\/annurev.bi.52.070183.003431","article-title":"Glutathione.","volume":"52","author":"A Meister","year":"1983","journal-title":"Annu Rev Biochem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1093\/emboj\/16.11.3057","article-title":"Co-amplification of the gamma-glutamylcysteine synthetase gene <italic>gsh1<\/italic> and of the ABC transporter gene <italic>pgpA<\/italic> in arsenite-resistant <italic>Leishmania tarentolae<\/italic>.","volume":"16","author":"K Grondin","year":"1997","journal-title":"EMBO J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1179\/000349803225002499","article-title":"<italic>Leishmania<\/italic>\/HIV co-infections: epidemiology in Europe.","volume":"97","author":"P Desjeux","year":"2003","journal-title":"Ann Trop Med Parasitol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1086\/587899","article-title":"Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome.","volume":"46","author":"R ter Horst","year":"2008","journal-title":"Clin Infect Dis"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1517\/14728210903153862","article-title":"Developments in the treatment of visceral leishmaniasis.","volume":"14","author":"ML den Boer","year":"2009","journal-title":"Expert Opin Emerg Drugs"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1179\/000349803225002516","article-title":"HIV and the transmission of <italic>Leishmania<\/italic>.","volume":"97","author":"R Molina","year":"2003","journal-title":"Ann Trop Med Parasitol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1086\/510398","article-title":"HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic mainstay in the treatment of leishmaniasis.","volume":"195","author":"C Barat","year":"2007","journal-title":"J Infect Dis"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.2165\/00003088-200544120-00005","article-title":"High variability of indinavir and nelfinavir pharmacokinetics in HIV-infected patients with a sustained virological response on highly active antiretroviral therapy.","volume":"44","author":"C Goujard","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1097\/00002030-200104130-00002","article-title":"Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport.","volume":"15","author":"K Jones","year":"2001","journal-title":"AIDS"},{"key":"ref42","first-page":"233","article-title":"Apoptosis in <italic>Leishmania<\/italic> species &amp; its relevance to disease pathogenesis.","volume":"123","author":"C Shaha","year":"2006","journal-title":"Indian J Med Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1128\/EC.00123-07","article-title":"Characterization of metacaspases with trypsin-like activity and their putative role in programmed cell death in the protozoan parasite <italic>Leishmania<\/italic>.","volume":"6","author":"N Lee","year":"2007","journal-title":"Eukaryot Cell"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exppara.2006.10.007","article-title":"Miltefosine induces apoptosis in arsenite-resistant <italic>Leishmania donovani<\/italic> promastigotes through mitochondrial dysfunction.","volume":"116","author":"NK Verma","year":"2007","journal-title":"Exp Parasitol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"5966","DOI":"10.1128\/JVI.76.12.5966-5973.2002","article-title":"Effects of antiretroviral drugs on human immunodeficiency virus type 1-induced CD4(+) T-cell death.","volume":"76","author":"J Estaquier","year":"2002","journal-title":"J Virol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.tips.2005.03.006","article-title":"Mitochondria are sensors for HIV drugs.","volume":"26","author":"F Petit","year":"2005","journal-title":"Trends Pharmacol Sci"}],"container-title":["PLoS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0000642","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T08:27:41Z","timestamp":1635150461000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0000642"}},"subtitle":[],"editor":[{"given":"Pierre","family":"Buffet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,3,30]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,3,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0000642","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,30]]}}}