title: Association of the Endobiont Double-Stranded RNA Virus LRV1 With Treatment Failure for Human Leishmaniasis Caused by Leishmania braziliensis in Peru and Bolivia.
abstract: Cutaneous and mucosal leishmaniasis, caused in South America by Leishmania braziliensis, is difficult to cure by chemotherapy (primarily pentavalent antimonials [Sb(V)]). Treatment failure does not correlate well with resistance in vitro, and the factors responsible for treatment failure in patients are not well understood. Many isolates of L. braziliensis (>25%) contain a double-stranded RNA virus named Leishmaniavirus 1 (LRV1), which has also been reported in Leishmania guyanensis, for which an association with increased pathology, metastasis, and parasite replication was found in murine models. Here we probed the relationship of LRV1 to drug treatment success and disease in 97 L. braziliensis-infected patients from Peru and Bolivia. In vitro cultures were established, parasites were typed as L. braziliensis, and the presence of LRV1 was determined by reverse transcription-polymerase chain reaction, followed by sequence analysis. LRV1 was associated significantly with an increased risk of treatment failure (odds ratio, 3.99; P = .04). There was no significant association with intrinsic Sb(V) resistance among parasites, suggesting that treatment failure arises from LRV1-mediated effects on host metabolism and/or parasite survival. The association of LRV1 with clinical drug treatment failure could serve to guide more-effective treatment of tegumentary disease caused by L. braziliensis.
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia Unidad de Pathoantigenos.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Adaui
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lon-Fye
authors.initials: LF
authors.lastname: Lye
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Akopyants
authors.affiliation: Unidad de Bioinformática, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Llanos-Cuentas
authors.affiliation: Laboratorio de Biología Molecular-IIBISMED, Facultad de Medicina, Universidad Mayor de San Simón, Cochabamba, Bolivia.
authors.forename: Lineth
authors.initials: L
authors.lastname: Garcia
authors.affiliation: Molecular Parasitology Unit, Institute of Tropical Medicine Antwerp.
authors.forename: Ilse
authors.initials: I
authors.lastname: Maes
authors.affiliation: Molecular Parasitology Unit, Institute of Tropical Medicine Antwerp.
authors.forename: Simonne
authors.initials: S
authors.lastname: De Doncker
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Dobson
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia Unidad de Pathoantigenos.
authors.forename: Jorge
authors.initials: J
authors.lastname: Arevalo
authors.affiliation: Molecular Parasitology Unit, Institute of Tropical Medicine Antwerp Department of Biomedical Sciences, University of Antwerp, Belgium.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley
mesh_terms: D000965:Antimony / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D001838:Bolivia / Q000453:epidemiology; D015331:Cohort Studies; D004351:Drug Resistance; D006801:Humans; D007892:Leishmania braziliensis / Q000821:virology*; D007897:Leishmaniasis, Mucocutaneous / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology / Q000821:virology*; D019199:Leishmaniavirus / Q000145:classification / Q000235:genetics; D010568:Peru / Q000453:epidemiology; D017211:Treatment Failure
chemical_list: D000981:Antiprotozoal Agents; D000965:Antimony
keywords: L. braziliensis; RNA viruses; Totivirus; Viannia; antimony drug treatment; drug resistance; drug treatment failure; leishmaniasis