Skip to main content

Advertisement

Log in

Leptomonas seymouri narna-like virus 1 and not leishmaniaviruses detected in kala-azar samples from India

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

The great majority of kala-azar/visceral leishmaniasis (VL) cases, which are caused by Leishmania donovani (LD), are reported in Asia. We investigated whether leishmaniaviruses (LRVs) are present in LD isolates. These dsRNA viruses contribute to hyperpathogenicity, as observed in the case of other members of the genus Leishmania. However, LRVs could not be detected in 22 Indian LD isolates tested in the present study, while 70% of these original LD isolates harboured a virus that was not of LD but instead of Leptomonas seymouri (LS) origin. LS is another protozoon that parasitizes the sandfly vector of LD. Historically, LD clinical isolates from India often showed high incidence of LS coinfection. LS was detected in 20 out of the 22 (91%) above-mentioned LD isolates. Leptomonas seymouri narna-like virus 1 (Lepsey NLV1) was identified by whole-genome sequencing in an LD-LS coinfected sample, and its presence was confirmed by PCR and sequencing in 15 (75%) of the 20 LD-LS coinfected samples. The LS-negative LD samples were also virus negative by PCR. That the human host is exposed to an RNA virus in LS, another coinfecting parasite with LD, i.e., the “LD-LS-Lepsey NLV1 triple pathogen” phenomenon, unveils a new paradigm of research towards revisiting the mysteries of Indian leishmaniasis pathogenesis and management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. World Health Organization (2010) Control of the leishmaniases. World Health Organ Tech Rep Ser xii–xiii:1–186

    Google Scholar 

  2. Thakur CP, Sinha GP, Pandey AK, Barat D, Sinha PK (1993) Amphotericin B in resistant kala-azar in Bihar. Natl Med J India 6(2):57–60

    CAS  PubMed  Google Scholar 

  3. Srivastava P, Prajapati VK, Vanaerschot M, Auwera GV, Dujardin JC, Sundar S (2010) Detection of Leptomonas sp. parasites in clinical isolates of Kalaazar patients from India. Infect Genet Evol 10(7):1145–1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ghosh S, Banerjee P, Sarkar A, Datta S, Chatterjee M (2012) Coinfection of Leptomonas seymouri and Leishmania donovani in Indian Leishmaniasis. J Clin Microbiol 50(8):2774–2778

    Article  PubMed  PubMed Central  Google Scholar 

  5. Singh N, Chikara S, Sundar S (2013) SOLiD Sequencing of genomes of clinical isolates of Leishmania donovani from India confirm Leptomonas co-infection and raise some key questions. PLoS ONE 8(2):e55738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kraeva N, Butenko A, Hlaváčová J, Kostygov A, Myškova J, Grybchuk D, Leštinová T, Votýpka J, Volf P, Opperdoes F, Flegontov P, Lukeš J, Yurchenko V (2015) Leptomonas seymouri: adaptations to the dixenous life cycle analyzed by genome sequencing, transcriptome profiling and co-infection with Leishmania donovani. PLoS Pathog 11(8):e1005127

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tarr PI, Aline RF Jr, Smiley BL, Scholler J, Keithly J (1988) LR1: a candidate RNA virus of Leishmania. Proc Natl Acad Sci USA 85:9572–9575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ives A, Ronet C, Prevel F, Ruzzante G, Fuertes-Marraco S, Schutz F, Zangger H, Revaz-Breton M, Lye L-F, Hickerson SM, Beverley SM, Acha-Orbea H, Launois P, Fasel N, Masina S (2011) Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science 331:775–778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cantanhêde LM, da Silva Júnior CF, Ito MM, Felipin KP, Nicolete R, Salcedo JMV, Porrozzi R, Cupolillo E, Ferreira RGM (2015) Further evidence of an association between the presence of Leishmania RNA virus 1 and the mucosal manifestations in tegumentary leishmaniasis patients. PLoS Negl Trop Dis 9(9):e0004079

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ito MM, Catanhêde LM, Katsuragawa TH, da Silva JCF, Camargo ALM, Mattos RG, Vilallobos-Salcedob JM (2015) Correlation between presence of Leishmania RNA virus 1 and clinical characteristics of nasal mucosal leishmaniosis. Braz J Otorhinolaryngol 81(5):533–540

    Article  PubMed  Google Scholar 

  11. Ginouves M, Simon S, Bourreau E, Lacoste V, Ronet C, Couppié P, Nacher M, Demar M, Prévot G (2016) Prevalence and distribution of Leishmania RNA virus 1 in Leishmania parasites from French Guiana. Am J Trop Med Hyg 94:102–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Scheffter SM, Ro YT, Chung IK, Patterson JL (1995) The complete sequence of Leishmania RNA virus LRV2-1, a virus of an Old World parasite strain. Virology 212:84–90

    Article  CAS  PubMed  Google Scholar 

  13. Zangger H, Hailu A, Desponds C, Lye L-F, Akopyants NS, Dobson DE, Ronet C, Ghalib H, Beverley SM, Fasel N (2014) Leishmania aethiopica field isolates bearing an endosymbiontic dsRNA virus induce pro-inflammatory cytokine response. PLoS Negl Trop Dis 8(4):e2836

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hajjaran H, Mahdi M, Mohebali M, Samimi-Rad K, Ataei-Pirkooh A, Kazemi-Rad E, Naddaf SR, Raoofian R (2016) Detection and molecular identification of leishmania RNA virus (LRV) in Iranian Leishmania species. Arch Virol 161(12):3385–3390

    Article  CAS  PubMed  Google Scholar 

  15. Hartley M-A, Ronet C, Zangger H, Beverley SM, Fasel N (2012) Leishmania RNA virus: when the host pays the toll. Front Cell Inf Microbiol 2:99

    Article  Google Scholar 

  16. Rossi M, Castiglioni P, Hartley MA, Eren RO, Prével F, Desponds C, Utzschneider DT, Zehn D, Cusi MG, Kuhlmann FM, Beverley SM, Ronet C, Fasel N (2017) Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis. Proc Natl Acad Sci USA 114(19):4987–4992

    Article  CAS  PubMed  Google Scholar 

  17. Ronet C, Ives A, Bourreau E, Fasel N, Launois P, Masina S (2010) Immune responses to Leishmania guyanensis infection in humans and animal models. Bentham Ebook Immune Res Parasit Infect 1:165–176

    CAS  Google Scholar 

  18. Adaui V, Lye LF, Akopyants NS, Zimic M, Llanos-Cuentas A, Garcia L, Maes I, De Doncker S, Dobson DE, Arevalo J, Dujardin JC, Beverley SM (2015) Association of the endobiont doubled-stranded RNA virus LRV1 with treatment failure of human leishmaniasis caused by Leishmania braziliensis in Peru and Bolivia. J Infect Dis 213(1):112–121

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bourreau E, Ginouves M, Prevot G, Hartley MA, Gangneux JP, Robert-Gangneux F, Dufour J, Sainte-Marie D, Bertolotti A, Pratlong F, Martin R, Schütz F, Couppié P, Fasel N, Ronet C (2015) Presence of Leishmania-RNA virus in L. guyanensis parasites increases the risk of first-line treatment failure and symptomatic relapse. J Infect Dis 213(1):105–111

    Article  PubMed  Google Scholar 

  20. Mukhopadhyay R, Mukherjee S, Mukherjee B, Naskar K, Mondal D, Decuypere S, Ostyn B, Prajapati VK, Sundar S, Dujardin JC, Roy S (2011) Characterisation of antimony-resistant Leishmania donovani isolates: biochemical and biophysical studies and interaction with host cells. Int J Parasitol 41(13–14):1311–1321

    Article  CAS  PubMed  Google Scholar 

  21. Khanra S, Saraf NR, Das S, Das AK, Roy S, Manna M (2016) Genetic markers for antimony resistant clinical isolates differentiation from Indian Kala-azar. Acta Tropica 164:177–184

    Article  CAS  PubMed  Google Scholar 

  22. Imamura H, Downing T, Van den Broeck F, Sanders MJ, Rijal S, Sundar S, Mannaert A, Vanaerschot M, Berg M, De Muylder G, Dumetz F, Cuypers B, Maes I, Domagalska M, Decuypere S, Rai K, Uranw S, Bhattarai NR, Khanal B, Prajapati VK, Sharma S, Stark O, Schönian G, De Koning HP, Settimo L, Vanhollebeke B, Roy S, Ostyn B, Boelaert M, Maes L, Berriman M, Dujardin JC, Cotton JA (2016) Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent. Elife 5:e12613

    Article  PubMed  PubMed Central  Google Scholar 

  23. Andrews S (2010) FastQC: A quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc. Accessed 4 May 2017

  24. Simpson JT, Durbin R (2012) Efficient de novo assembly of large genomes using compressed data structures. Genome Res 22:549–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lassmann T, Hayashizaki Y, Daub CO (2009) TagDust—a program to eliminate artifacts from next generation sequencing data. Bioinformatics 25:2839–2840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, Pyshkin AV (2012) SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comp Biol 19(5):455–477

    Article  CAS  Google Scholar 

  27. Besemer J, Borodovsky M (2005) GeneMark: web software for gene finding in prokaryotes, eukaryotes and viruses. Nucleic Acids Res 33(2):W451–W454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Srivastava P, Mehrotra S, Tiwary P, Chakravarty J, Sundar S (2011) Diagnosis of Indian visceral leishmaniasis by nucleic acid detection using PCR. PLoS ONE 6(4):e19304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Weirather JL, Jeronimo SM, Gautam S, Sundar S, Kang M, Kurtz MA, Haque R, Schriefer A, Talhari S, Carvalho EM, Donelson JE, Wilson ME (2011) Serial quantitative PCR assay for detection, species discrimination, and quantification of Leishmania spp. in human samples. J Clin Microbiol 49:3892–3904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zangger H, Ronet C, Desponds C, Kuhlmann FM, Robinson J, Hartley MA, Prevel F, Castiglioni P, Pratlong F, Bastien P, Muller N, Parmentier L, Saravia NG, Beverley SM, Fasel N (2013) Detection of Leishmania RNA virus in Leishmania parasites. PLoS Negl Trop Dis 7(1):e2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Selvapandiyan A, Ahuja K, Puri N, Krishnan A (2015) Implications of co-infection of Leptomonas in visceral leishmaniasis in India. Parasitology 142(14):1657–1662

    Article  PubMed  Google Scholar 

  32. Lye LF, Akopyants NS, Dobson DE, Beverley SM (2016) A Narnavirus element from the Trypanosomatid protozoan parasite Leptomonas seymouri. Genome Announc. 4(4):e00713–e00716

    Article  PubMed  PubMed Central  Google Scholar 

  33. Fichorova RN, Lee Y, Yamamoto HS, Takagi Y, Hayes GR, Goodman RP, Chepa-Lotrea X, Buck OR, Murray R, Kula T, Beach DH, Singh BN, Nibert ML (2012) Endobiont viruses sensed by the human host—beyond conventional antiparasitic therapy. PLoS ONE 7:e48418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hartley M-A, Ronet C, Fasel N (2012) Backseat drivers: the hidden influence of microbial viruses on disease. Curr Opin Microbiol 15:1–8

    Article  Google Scholar 

  35. Mukhopadhyay D, Dalton JE, Kaye PM, Chatterjee M (2014) Post kala-azar dermal leishmaniasis: an unresolved mystery. Trends Parasitol 30(2):65–74

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bonifati C, Lora V, Graceffa D, Nosotti L (2016) Management of psoriasis patients with hepatitis B or hepatitis C virus infection. World J Gastroenterol 22:6444–6455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kuhlmann FM, Robinson JI, Bluemling GR, Ronet C, Fasel N, Beverley SM (2017) Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor. Proc Natl Acad Sci USA 114(5):E811–E819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Castiglioni P, Hartley M-A, Rossi M, Prevel F, Desponds C, Utzschneider DT, Eren RO, Zangger H, Brunner L, Collin N, Zehn D, Kuhlmann FM, Beverley SM, Fasel N, Ronet C (2017) Exacerbated Leishmaniasis caused by a viral endosymbiont can be prevented by immunization with its viral capsid. PLoS Negl Trop Dis 11(1):e0005240

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge Dr. Madhumita Manna, Bidhannagar College, Kolkata, for access to the clinical isolates T2 and T8. The authors acknowledge CSIR-IICB for providing laboratory facilities for conducting the present work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Subhajit Biswas.

Ethics declarations

Funding

The project was funded by a Grant from the Council of Scientific and Industrial Research (CSIR) (grant BSC0114) and a J.C. Bose Fellowship (SB/S2/JCB-65/2014). S. Sukla was supported by CSIR’s Scientists’ Pool Scheme.

Conflict of interest

The authors declare no competing financial interests.

Ethical approval and informed consent

This study was performed in accordance with the ethical standards (at par with the 1964 Helsinki declaration and its later amendments) of the review boards of all relevant institutions. Informed consent was obtained from all individual participants included in the original study. All experiments were carried out in accordance with the relevant guidelines and regulations.

Additional information

Handling editor: Tim Skern.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 46 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sukla, S., Roy, S., Sundar, S. et al. Leptomonas seymouri narna-like virus 1 and not leishmaniaviruses detected in kala-azar samples from India. Arch Virol 162, 3827–3835 (2017). https://doi.org/10.1007/s00705-017-3559-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-017-3559-y

Navigation