Association of the endobiont double-Stranded RNA virus LRV1 with treatment failure for human leishmaniasis caused by Leishmania braziliensis in Peru and Bolivia

Vanessa Adaui, Lon-Fye Lye, Natalia S Akopyants, Mirko Zimic, Alejandro Llanos-Cuentas, Lineth Garcia, Ilse Maes, Simonne De Doncker, Deborah E Dobson, Jorge Arevalo, Jean-Claude Dujardin, Stephen M Beverley

Research output: Contribution to journalA1: Web of Science-article

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.

Original languageEnglish
JournalJournal of Infectious Diseases
Volume213
Issue number1
Pages (from-to)112-121
Number of pages10
ISSN0022-1899
DOIs
Publication statusPublished - 2016

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