Ausência de relação na susceptibilidade in vitro de promastigotas de Leishmania (Viannia) braziliensis e de Leishmania RNA virus 1 ao antimonial trivalente
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May 22, 2025
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Resumo
Objetivo: Avaliar a relação entre a presença/carga viral do Leishmania RNA virus 1 (LRV1) e a susceptibilidade in vitro de promastigotas de Leishmania (Viannia) braziliensis ao antimônio trivalente (SbIII). Métodos: Estudo experimental analisando 20 cepas de L. (V.) braziliensis, 12 positivas para LRV1. A susceptibilidade ao SbIII foi avaliada por curvas de suavização e índice de atividade (IA). O LRV1 foi quantificado por PCR em tempo real (qPCR). Testes estatísticos foram aplicados para avaliar as associações e correlações entre os parâmetros analisados. Resultados: As cepas foram classificadas como suscetíveis (N=8) e menos suscetíveis (N=12) com base nas curvas de suavização em relação à cepa de referência. No IA, todas as cepas apresentaram menor susceptibilidade em comparação à referência. Das 12 cepas positivas para LRV1, 75% tiveram carga viral quantificada, enquanto 25% ficaram abaixo do limite de quantificação. As cepas LRV1 positivas exibiram maior densidade parasitária em relação as negativas. Conclusão: Embora as cepas LRV1 positivas apresentem maior densidade parasitária, não houve correlação significativa entre a presença/carga viral de LRV1 e a susceptibilidade in vitro ao SbIII.
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Como Citar
MedeirosE. H. R. T. de, MattosC. B., FialhoS. N., SilvaA. K. da C., SouzaC. L., TelesC. B. G., CantanhêdeL. M., RodriguesM. M. de S., FerreiraR. de G. M., & FerreiraG. E. M. (2025). Ausência de relação na susceptibilidade in vitro de promastigotas de Leishmania (Viannia) braziliensis e de Leishmania RNA virus 1 ao antimonial trivalente. Revista Eletrônica Acervo Saúde, 25(5), e20534. https://doi.org/10.25248/reas.e20534.2025
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Referências
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5. BACELLAR O, et al. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infection and immunity, 2002; 70(12): 6734-6740.
6. BERBERT TSN, et al. Pentavalent antimonials combined with other therapeutic alternatives for the treatment of cutaneous and mucocutaneous leishmaniasis: A systematic review. Dermatology research and practice. 2018; 9014726.
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13. CANTANHÊDE LM, et al. New insights into the genetic diversity of Leishmania RNA Virus 1 and its species-specific relationship with Leishmania parasites. PLoS ONE. 2018; 13(6): 198727.
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16. CASTELLUCCI LC, et al. Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil. Memorias do Instituto Oswaldo Cruz. 2014; 109(3): 279-288.
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18. CROFT SL, et al. Drug resistance in leishmaniasis. Clinical microbiology reviews. 2006; 19(1): 111-126.
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21. IVES A, et al. Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science. 2011; 331(6018): 775-778.
22. LEPROHON P, et al. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic acids research. 2009; 37(5): 1387-1399.
23. MATRANGOLO FSV, et al. Comparative proteomic analysis of antimony-resistant and-susceptible Leishmania braziliensis and Leishmania infantum chagasi lines. Molecular and biochemical parasitology. 2013; 190(2): 63-75.
24. MEIRA CS and GEDAMU L. Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis. Microorganisms. 2019; 7(12): 695.
25. MONCADA-DIAZ MJ, et al. Molecular Mechanisms of Drug Resistance in Leishmania spp. Pathogens. 2024; 13(10): 835.
26. MUKHERJEE A, et al. Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. Journal of Antimicrobial Chemotherapy. 2007; 59(2): 204-211.
27. PONTE-SUCRE A, et al. Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS neglected tropical diseases. 2017; 11(12): 6052.
28. RAMASAWMY R, et al. The− 2518 bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil. Infection, genetics and evolution, 2010; 10(5): 607-613.
29. REED GF, et al. Use of coefficient of variation in assessing variability of quantitative assays. Clinical and Vaccine Immunology. 2002; 9(6): 1235-1239.
30. ROJAS R, et al. Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. The Journal of infectious diseases. 2006; 193(10): 1375-1383.
31. ROMERO GAS, et al. Comparison of Cutaneous Leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in brazil: Therapeutic response to Meglumine Antimoniate. Am. J. Trop. Med. Hyg. 2001; 65: 456–465.
32. RUGANI JN, et al. Antimony resistance in Leishmania (Viannia) braziliensis clinical isolates from atypical lesions associates with increased ARM56/ARM58 transcripts and reduced drug uptake. Memórias do Instituto Oswaldo Cruz. 2019; 114: 190111.
33. SANTANA MCO, et al. Exploring Host-Specificity: Untangling the Relationship between Leishmania (Viannia) Species and Its Endosymbiont Leishmania RNA Virus 1. Microorganisms. 2023; 11(9): 2295.
34. SANTOS GA, et al. Systematic review of treatment failure and clinical relapses in leishmaniasis from a multifactorial perspective: Clinical aspects, factors associated with the parasite and host. Tropical Medicine and Infectious Disease. 2023; 8(9): 430.
35. SCHEFFTER SM, et al. The complete sequence of Leishmania RNA virus LRV2-1, a virus of an Old World parasite strain. Virology. 1995; 212: 84–90.
36. TARR PI, et al. LR1: a candidate RNA virus of Leishmania. Proceedings of the National Academy of Sciences of the United States of America. 1988; 85(24): 9572–5.
37. WHO. Leishmaniasis. Available at: https ://www.who.int/health-topics/leishmaniasis#tab=tab_1. Accessed on: July 15, 2024.
38. YARDLEY V, et al. American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug susceptibility? The Journal of infectious diseases. 2006; 194(8): 1168- 1175.
39. ZANGGER H, et al. Leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response. PLoS neglected tropical diseases. 2014; 8(4): 2836.
40. ZAULI-NASCIMENTO R, et al. In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B. Tropical Medicine & International Health. 2010; 15(1): 68-76.
2. ALVAR J, et al. Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 2012; 7(5): 35671.
3. ANDRADE JM, et al. Comparative transcriptomic analysis of antimony resistant and susceptible Leishmania infantum lines. Parasites & Vectors. 2020; 13(600): 1-15.
4. AREVALO J, et al. Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. The Journal of infectious diseases. 2007; 195(12): 1846-1851.
5. BACELLAR O, et al. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infection and immunity, 2002; 70(12): 6734-6740.
6. BERBERT TSN, et al. Pentavalent antimonials combined with other therapeutic alternatives for the treatment of cutaneous and mucocutaneous leishmaniasis: A systematic review. Dermatology research and practice. 2018; 9014726.
7. BIYANI N, et al. Differential expression of proteins in antimony-susceptible and-resistant isolates of Leishmania donovani. Molecular and biochemical parasitology. 2011; 179(2): 91-99.
8. BOURREAU E, et al. Presence of Leishmania RNA virus 1 in Leishmania guyanensis increases the risk of first-line treatment failure and symptomatic relapse. The Journal of infectious diseases. 2016; 213(1): 105-111.
9. BRASIL, Ministério da Saúde. Leishmaniose Tegumentar Americana - Casos Confirmados Notificados No Sistema De Informação De Agravos De Notificação - Brasil. 2022. Available at:
10. BROTHERTON MC, et al. Proteomic and Genomic Analyses of Antimony Resistant Leishmania infantum Mutant. PLoS ONE. 2013; 8(11): 81899.
11. BURZA S, et al. Leishmaniasis. The Lancet. 2018; 392(10151): 951-970.
12. CANTANHÊDE LM, et al. Further evidence of an association between the presence of Leishmania RNA virus 1 and the mucosal manifestations in tegumentary leishmaniasis patients. PLoS neglected tropical diseases, 2015; 9(9): 4079.
13. CANTANHÊDE LM, et al. New insights into the genetic diversity of Leishmania RNA Virus 1 and its species-specific relationship with Leishmania parasites. PLoS ONE. 2018; 13(6): 198727.
14. CARRION JR, et al. Leishmaniaviruses. Encyclopedia of Virology. 2008; 220–224.
15. CARVALHO RVH, et al. Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition. Nat Commun. 2019; 10: 5273.
16. CASTELLUCCI LC, et al. Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil. Memorias do Instituto Oswaldo Cruz. 2014; 109(3): 279-288.
17. CLEVELAND WS and DEVLIN SJ. Locally weighted regression: an approach to regression analysis by local fitting. Journal of the American statistical association. 1988; 83(403): 596-610.
18. CROFT SL, et al. Drug resistance in leishmaniasis. Clinical microbiology reviews. 2006; 19(1): 111-126.
19. GUILBRIDE L, et al. Distribution and sequence divergence of LRV1 viruses among different Leishmania species. Molecular and Biochemical Parasitology. 1992; 54(1): 101–104.
20. HYDE R. Dose response curve analysis. University of Glasglow. 2018. Available at: https ://bitbucket.org/russ H/pog_codeclub/src/HEAD/challenges/codeclub_05_ic50.Rmd. Accessed on: April 10, 2020.
21. IVES A, et al. Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science. 2011; 331(6018): 775-778.
22. LEPROHON P, et al. Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic acids research. 2009; 37(5): 1387-1399.
23. MATRANGOLO FSV, et al. Comparative proteomic analysis of antimony-resistant and-susceptible Leishmania braziliensis and Leishmania infantum chagasi lines. Molecular and biochemical parasitology. 2013; 190(2): 63-75.
24. MEIRA CS and GEDAMU L. Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis. Microorganisms. 2019; 7(12): 695.
25. MONCADA-DIAZ MJ, et al. Molecular Mechanisms of Drug Resistance in Leishmania spp. Pathogens. 2024; 13(10): 835.
26. MUKHERJEE A, et al. Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. Journal of Antimicrobial Chemotherapy. 2007; 59(2): 204-211.
27. PONTE-SUCRE A, et al. Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS neglected tropical diseases. 2017; 11(12): 6052.
28. RAMASAWMY R, et al. The− 2518 bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil. Infection, genetics and evolution, 2010; 10(5): 607-613.
29. REED GF, et al. Use of coefficient of variation in assessing variability of quantitative assays. Clinical and Vaccine Immunology. 2002; 9(6): 1235-1239.
30. ROJAS R, et al. Resistance to antimony and treatment failure in human Leishmania (Viannia) infection. The Journal of infectious diseases. 2006; 193(10): 1375-1383.
31. ROMERO GAS, et al. Comparison of Cutaneous Leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in brazil: Therapeutic response to Meglumine Antimoniate. Am. J. Trop. Med. Hyg. 2001; 65: 456–465.
32. RUGANI JN, et al. Antimony resistance in Leishmania (Viannia) braziliensis clinical isolates from atypical lesions associates with increased ARM56/ARM58 transcripts and reduced drug uptake. Memórias do Instituto Oswaldo Cruz. 2019; 114: 190111.
33. SANTANA MCO, et al. Exploring Host-Specificity: Untangling the Relationship between Leishmania (Viannia) Species and Its Endosymbiont Leishmania RNA Virus 1. Microorganisms. 2023; 11(9): 2295.
34. SANTOS GA, et al. Systematic review of treatment failure and clinical relapses in leishmaniasis from a multifactorial perspective: Clinical aspects, factors associated with the parasite and host. Tropical Medicine and Infectious Disease. 2023; 8(9): 430.
35. SCHEFFTER SM, et al. The complete sequence of Leishmania RNA virus LRV2-1, a virus of an Old World parasite strain. Virology. 1995; 212: 84–90.
36. TARR PI, et al. LR1: a candidate RNA virus of Leishmania. Proceedings of the National Academy of Sciences of the United States of America. 1988; 85(24): 9572–5.
37. WHO. Leishmaniasis. Available at: https ://www.who.int/health-topics/leishmaniasis#tab=tab_1. Accessed on: July 15, 2024.
38. YARDLEY V, et al. American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug susceptibility? The Journal of infectious diseases. 2006; 194(8): 1168- 1175.
39. ZANGGER H, et al. Leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response. PLoS neglected tropical diseases. 2014; 8(4): 2836.
40. ZAULI-NASCIMENTO R, et al. In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B. Tropical Medicine & International Health. 2010; 15(1): 68-76.