{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:51:44Z","timestamp":1780642304311,"version":"3.54.1"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T00:00:00Z","timestamp":1289260800000},"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.0000866","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T20:23:31Z","timestamp":1289334211000},"page":"e866","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":39,"title":["Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell\u2013Driven Protective Response"],"prefix":"10.1371","volume":"4","author":[{"given":"Dirlei","family":"Nico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Claser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara P.","family":"Borja-Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz R.","family":"Travassos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Palatnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"da Silva Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio Martins","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisa B.","family":"Palatnik-de-Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,11,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"9375","DOI":"10.1073\/pnas.0703678104","article-title":"Evolutionary and geographical history of the <italic>Leishmania donovani<\/italic> complex with a revision of current taxonomy.","volume":"104","author":"J Lukes","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ijpara.2006.03.006","article-title":"Towards multilocus sequence typing of the <italic>Leishmania donovani<\/italic> complex: resolving genotypes and haplotypes for five polymorphic metabolic enzymes (ASAT, GPI, NH1, NH2, PGD).","volume":"36","author":"IL Mauricio","year":"2006","journal-title":"Int J Parasitol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.1021\/bi952998u","article-title":"Inosine-uridine nucleoside hydrolase from <italic>Crithidia fasciculata<\/italic>. Genetic characterization, crystallization, and identification of histidine 241 as a catalytic site residue.","volume":"35","author":"DN Gopaul","year":"1996","journal-title":"Biochemistry"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1074\/jbc.273.4.2118","article-title":"Molecular cloning and expression of a purine-specific N-ribohydrolase from <italic>Trypanosoma brucei brucei<\/italic>. Sequence, expression and molecular analysis.","volume":"273","author":"R Pell\u00e9","year":"1998","journal-title":"J Biol Chem"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1016\/S0021-9258(17)42957-7","article-title":"Nucleoside Hydrolase from <italic>Trypanosoma cruzi<\/italic>.","volume":"259","author":"RL Miller","year":"1984","journal-title":"J Biol Chem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"21114","DOI":"10.1074\/jbc.274.30.21114","article-title":"Nucleoside hydrolase from <italic>Leishmania major<\/italic>. Cloning, expression, catalytic properties, transition state inhibitors, and the 2.5-\u00c5 crystal structure.","volume":"274","author":"W Shi","year":"1999","journal-title":"J Biol Chem"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0378-1119(01)00768-5","article-title":"A nonspecific nucleoside hydrolase from <italic>Leishmania donovani<\/italic>: implications for purine salvage by the parasite.","volume":"280","author":"L Cui","year":"2001","journal-title":"Gene"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0166-6851(02)00010-5","article-title":"Nucleoside hydrolase from <italic>Leishmania (L.) donovani<\/italic> is an antigen diagnostic for visceral leishmaniasis.","volume":"120","author":"DM Santana","year":"2002","journal-title":"Mol Biochem Parasitol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1021\/bi702448s","article-title":"Structural basis for substrate specificity in group I nucleoside hydrolases.","volume":"47","author":"E Iovane","year":"2008","journal-title":"Biochemistry"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1128\/JB.185.11.3373-3378.2003","article-title":"Genes of <italic>Bacillus cereus<\/italic> and <italic>Bacillus anthracis<\/italic> encoding proteins of the exosporium.","volume":"185","author":"SJ Todd","year":"2003","journal-title":"J Bacteriol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1128\/AEM.68.3.1336-1343.2002","article-title":"<italic>Saccharomyces cerevisiae<\/italic> URH1 (encoding uridine-cytidine N-ribohydrolase): functional complementation by a nucleoside hydrolase from a protozoan parasite and by a mammalian uridine phosphorylase.","volume":"68","author":"R Mitterbauer","year":"2002","journal-title":"Appl Environ Microbiol"},{"key":"ref12","year":"1997"},{"key":"ref13","article-title":"BLAST - National Institutes of Health (NIH).","volume":"9"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1128\/IAI.73.2.812-819.2005","article-title":"Cross-protective efficacy of a prophylactic <italic>Leishmania donovani<\/italic> DNA vaccine against visceral and cutaneous murine leishmaniasis.","volume":"73","author":"I Aguilar-Be","year":"2005","journal-title":"Infec Immun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1051\/parasite\/2009163227","article-title":"A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoprotein 63 protects female but not male hamsters against Leishmania mexicana.","volume":"16","author":"WG Chal\u00e9-Balboa","year":"2009","journal-title":"Parasite"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.provac.2009.07.022","article-title":"The Nucleoside hydrolase DNA vaccine VR1012NH36 in prophylactic vaccination against mice tegumentar leishmaniasis.","volume":"1","author":"LOP Souza","year":"2009","journal-title":"Proc Vaccinol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.4269\/ajtmh.2007.77.1060","article-title":"Protection of susceptible BALB\/c mice from challenge with <italic>Leishmania major<\/italic> by nucleoside hydrolase, a soluble exo-antigen of <italic>Leishmania<\/italic>.","volume":"77","author":"MA Al-Wabel","year":"2007","journal-title":"Am J Trop Med Hyg"},{"key":"ref18","first-page":"1068","article-title":"A Phase III trial of Efficacy of the FML- vaccine against canine kala-azar in an endemic area of Brazil (S\u00e3o Gon\u00e7alo do Amarante, RN).","volume":"19","author":"VO da Silva","year":"2001","journal-title":"Vaccine"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"4991","DOI":"10.1016\/j.vaccine.2008.07.029","article-title":"Immunogenicity assay of the Leishmune vaccine against canine visceral leishmaniasis in Brazil.","volume":"26","author":"GP Borja-Cabrera","year":"2008","journal-title":"Vaccine"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1586\/14760584.7.6.833","article-title":"The FML-vaccine against canine visceral leishmaniasis: from the second generation to the synthetic vaccine.","volume":"7","author":"CB Palatnik-de-Sousa","year":"2008","journal-title":"Exp Rev Vaccines"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1016\/j.vaccine.2005.11.061","article-title":"The FML-vaccine (Leishmune) against canine visceral leishmaniasis: a transmission blocking vaccine.","volume":"24","author":"EM Saraiva","year":"2006","journal-title":"Vaccine"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1016\/j.vaccine.2009.03.045","article-title":"Decrease of the incidence of human and canine visceral leishmaniasis after dog vaccination with Leishmune in Brazilian endemic areas.","volume":"27","author":"CB Palatnik-de-Sousa","year":"2009","journal-title":"Vaccine"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1590\/S0037-86821996000200008","article-title":"The FML (Fucose Mannose Ligand) of <italic>Leishmania donovani<\/italic>. A new tool in diagnosis, prognosis, transfusional control and vaccination against human Kala-azar.","volume":"29","author":"CB Palatnik-de-Sousa","year":"1996","journal-title":"Rev Soc Bras Med Trop"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0001-706X(93)90006-W","article-title":"<italic>Leishmania donovani<\/italic> surface glycoproteins GP36, is the major immunogen component of the Fucose Mannose Ligand (FML).","volume":"53","author":"CB Palatnik de Sousa","year":"1993","journal-title":"Acta Trop"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1016\/S0264-410X(01)00031-7","article-title":"Vaccination of Balb\/c mice against experimental visceral leishmaniasis with the GP36 glycoprotein antigen of <italic>Leishmania donovani<\/italic>.","volume":"19","author":"E Paraguai de Souza","year":"2001","journal-title":"Vaccine"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.provac.2009.07.019","article-title":"Nucleoside hydrolase DNA vaccine against visceral leishmaniasis.","volume":"1","author":"GP Borja-Cabrera","year":"2009","journal-title":"Proc Vaccinol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1016\/j.vaccine.2006.03.005","article-title":"Immunotherapy against visceral leishmaniasis with the nucleoside hydrolase-DNA vaccine of <italic>L. donovani<\/italic>.","volume":"24","author":"R Gamboa-Le\u00f3n","year":"2006","journal-title":"Vaccine"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.provac.2009.07.021","article-title":"Cloning of the Nucleoside hydrolase of <italic>Leishmania donovani<\/italic> aiming at the development of a synthetic vaccine against visceral leishmaniasis.","volume":"1","author":"D Nico","year":"2009","journal-title":"Proc Vaccinol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1747-0285.2009.00825.x","article-title":"Advantages of a synthetic peptide immunogen over a protein immunogen in the Development of an anti-pilus vaccine for <italic>Pseudomonas aeruginosa<\/italic>.","volume":"74","author":"DJ Kao","year":"2009","journal-title":"Biol Drug Res"},{"key":"ref30","first-page":"14907","article-title":"Major Histocompatibility Complex and T cell interactions of a universal T-cell epitope from <italic>Plasmodium falciparum<\/italic> circumsporozoite protein.","volume":"281","author":"C Parra-L\u00f3pez","year":"2006"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4049\/jimmunol.151.1.489","article-title":"CD4+ T cell clones obtained from <italic>Plasmodium falciparum<\/italic> sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein.","volume":"151","author":"A Moreno","year":"1993","journal-title":"J Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1016\/j.vaccine.2006.02.034","article-title":"Acylated and deacylated saponins of <italic>Quillaja saponaria<\/italic> mixture as adjuvants for the FML-vaccine against visceral leishmaniasis.","volume":"24","author":"E Oliveira-Freitas","year":"2006","journal-title":"Vaccine"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0264-410X(02)00444-9","article-title":"Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis.","volume":"21","author":"WR Santos","year":"2002","journal-title":"Vaccine"},{"key":"ref34","first-page":"290","article-title":"Vaccination with the FML antigen (Fucose Mannose Ligand) of <italic>Leishmania donovani<\/italic> protects hamsters from experimental Visceral Leishmaniasis.","volume":"46","author":"CB Palatnik de Sousa","year":"1994","journal-title":"J Braz Soc Adv Sci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.vetpar.2006.06.028","article-title":"Leishmania DNA load and cytokine expression levels in asymptomatic naturally infected dogs.","volume":"142","author":"L Manna","year":"2006","journal-title":"Vet Parasitol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.181.1.387","article-title":"Interleukin 12 is effective treatment for an established systemic intracellular infection: experimental visceral leishmaniasis.","volume":"181","author":"HW Murray","year":"1995","journal-title":"J Exp Med"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1084\/jem.185.7.1231","article-title":"Intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-gamma gene-disrupted mice.","volume":"185","author":"AP Taylor","year":"1997","journal-title":"J Exp Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.4049\/jimmunol.0900276","article-title":"Intracellular replication-deficient <italic>Leishmania donovani<\/italic> induces long-lasting protective immunity against visceral leishmaniasis.","volume":"183","author":"A Selvapandiyan","year":"2009","journal-title":"J Immunol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.vaccine.2009.10.053","article-title":"Innate immune defense in visceral leishmaniasis: cytokine mediates protective role by allogeneic effector cells.","volume":"28","author":"PP Manna","year":"2010","journal-title":"Vaccine"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.4049\/jimmunol.145.12.4306","article-title":"Tumor necrosis factor-\u03b1 synergizes with IFN-\u03b3 in mediating killing of <italic>Leishmania major<\/italic> through the induction of nitric oxide.","volume":"145","author":"FY Liew","year":"1990","journal-title":"J Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.vetimm.2008.11.020","article-title":"Expression of IFN\u03b3, TNF\u03b1, IL-10 and TGF\u03b2 in lymph nodes associates with parasite load and clinical form of disease in dogs naturally infected with <italic>Leishmania (Leishmania) chagasi<\/italic>.","volume":"128","author":"CF Alves","year":"2009","journal-title":"Vet Immunol Immunopathol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.vetimm.2008.04.010","article-title":"Longitudinal analysis of cytokine gene expression and parasite load in PBMC in <italic>Leishmania infantum<\/italic> experimentally infected dogs.","volume":"125","author":"E Sanchez-Robert","year":"2008","journal-title":"Vet Immunol Immunopathol"},{"key":"ref43","first-page":"502","article-title":"Visceral leishmaniasis and anti TNF\u03b1 therapy: case report and review of literature.","volume":"27","author":"F De Leonardis","year":"2009","journal-title":"Clin Exp Rheumatol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1128\/IAI.69.8.4719-4725.2001","article-title":"<italic>Leishmania donovani<\/italic> p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis.","volume":"69","author":"PC Melby","year":"2001","journal-title":"Infect Immun"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.ppat.1000813","article-title":"Innate Killing of <italic>Leishmania donovani<\/italic> by Macrophages of the Splenic Marginal Zone Requires IRF-7.","volume":"6","author":"R Phillips","year":"2010","journal-title":"Plos Pathogens"},{"key":"ref46","first-page":"247","article-title":"T cell quality in memory and protection: implications for vaccine design.","volume":"8","author":"RA Seder","year":"2008","journal-title":"Nature Rev"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nm1592","article-title":"Multifunctional T<sub>H<\/sub>1 cells define a correlate of vaccine-mediated protection against Leishmania major.","volume":"13","author":"PA Darrah","year":"2007","journal-title":"Nat Medicine"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.exppara.2008.06.004","article-title":"Leishmania (Leishmania) amazonensis: experimental cutaneous leishmaniasis associated with systemic amyloidosis in mice.","volume":"120","author":"LO Carvalho","year":"2008","journal-title":"Exp Parasitol"},{"key":"ref49","first-page":"117","article-title":"Parasite cysteine proteinase interactions with alpha 2-macroglobulin or kininogens: differential pathways modulating inflammation and innate immunity in infection by pathogenic typanosomatids.","volume":"211","author":"J Scharfetsin","year":"2005","journal-title":"Immunobiology"},{"key":"ref50","article-title":"Histopathological analysis of initial cellular response in TLR-2 deficient mice experimentally infected by <italic>Leishmania (L.) amazonensis<\/italic>.","author":"CS Guerra","year":"2010"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.1128\/IAI.71.7.3988-3994.2003","article-title":"Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis infection.","volume":"71","author":"EA Coelho","year":"2003","journal-title":"Inf Immun"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/S1359-6446(03)02864-2","article-title":"Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity.","volume":"8","author":"DJ Marciani","year":"2003","journal-title":"Drug Discov Today"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.vaccine.2008.01.023","article-title":"Vaccines for leishmaniasis in the fore coming 25 years. Review.","volume":"26","author":"CB Palatnik-de-Sousa","year":"2008","journal-title":"Vaccine"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1086\/513439","article-title":"HLA class I-restricted T cell epitopes of the kinetoplastid membrane protein-11 presented by <italic>Leishmania donovani<\/italic>-infected human macrophages.","volume":"195","author":"R Basu","year":"2007","journal-title":"J Infect Dis"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"7036","DOI":"10.1016\/j.vaccine.2009.09.066","article-title":"Optimized subunit vaccine protects against experimental leishmaniasis.","volume":"27","author":"S Bertholet","year":"2009","journal-title":"Vaccine"}],"container-title":["PLoS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0000866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T04:49:24Z","timestamp":1685854164000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0000866"}},"subtitle":[],"editor":[{"given":"Christian R.","family":"Engwerda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,11,9]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2010,11,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0000866","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,9]]}}}