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A new densovirus in cerebrospinal fluid from a case of anti-NMDA-receptor encephalitis

Archives of Virology volume 161, pages 3231–3235 (2016)Cite this article

Abstract

We characterized the genome of a densovirus, tentatively called human CSF-associated densovirus 1 (HuCSFDV1), in cerebrospinal fluid (CSF) from a human case of encephalitis with antibodies against the N-methyl D-aspartate receptor. The presence of the viral genome in CSF was independently confirmed. This virus, which is proposed to be a member of a new species in the genus Iteradensovirus of the subfamily Densovirinae, showed the typical two ORFs encoding nonstructural and structural proteins with low-level identities of 22 and 16 % to the closest known densovirus relative. No other eukaryotic viral sequences were detected using deep sequencing. The replication and pathogenicity in humans of this virus, which belongs to a viral subfamily whose members are only known to replicate in invertebrates, remain to be demonstrated. Alternative explanations for the detection of densovirus DNA in CSF are discussed.

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References

  1. Armangue T, Titulaer MJ, Malaga I, Bataller L, Gabilondo I, Graus F, Dalmau J (2013) Pediatric anti-N-methyl-d-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 162(850–856):e852

    Google Scholar 

  2. Bergoin M, Tijssen P (2000) Molecular biology of Densovirinae. Contrib Microbiol 4:12–32

    Article  CAS  PubMed  Google Scholar 

  3. Carlson J, Suchman E, Buchatsky L (2006) Densoviruses for control and genetic manipulation of mosquitoes. Adv Virus Res 68:361–392

    Article  CAS  PubMed  Google Scholar 

  4. Cotmore SF, Agbandje-McKenna M, Chiorini JA, Mukha DV, Pintel DJ, Qiu J, Soderlund-Venermo M, Tattersall P, Tijssen P, Gatherer D, Davison AJ (2014) The family Parvoviridae. Arch Virol 159:1239–1247

    Article  CAS  PubMed  Google Scholar 

  5. Dalmau J, Tuzun E, Wu HY, Masjuan J, Rossi JE, Voloschin A, Baehring JM, Shimazaki H, Koide R, King D, Mason W, Sansing LH, Dichter MA, Rosenfeld MR, Lynch DR (2007) Paraneoplastic anti-N-methyl-d-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 61:25–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7:1091–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fediere G, Li Y, Zadori Z, Szelei J, Tijssen P (2002) Genome organization of Casphalia extranea densovirus, a new iteravirus. Virology 292:299–308

    Article  CAS  PubMed  Google Scholar 

  8. Ge X, Li Y, Yang X, Zhang H, Zhou P, Zhang Y, Shi Z (2012) Metagenomic analysis of viruses from bat fecal samples reveals many novel viruses in insectivorous bats in China. J Virol 86:4620–4630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gilbert GJ (2014) Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 82:2041

    Article  PubMed  Google Scholar 

  10. Gleichman AJ, Spruce LA, Dalmau J, Seeholzer SH, Lynch DR (2012) Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain. J Neurosci 32:11082–11094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hewson I, Button JB, Gudenkauf BM, Miner B, Newton AL, Gaydos JK, Wynne J, Groves CL, Hendler G, Murray M, Fradkin S, Breitbart M, Fahsbender E, Lafferty KD, Kilpatrick AM, Miner CM, Raimondi P, Lahner L, Friedman CS, Daniels S, Haulena M, Marliave J, Burge CA, Eisenlord ME, Harvell CD (2014) Densovirus associated with sea-star wasting disease and mass mortality. Proc Natl Acad Sci USA 111:17278–17283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ilyina TV, Koonin EV (1992) Conserved sequence motifs in the initiator proteins for rolling circle DNA replication encoded by diverse replicons from eubacteria, eucaryotes and archaebacteria. Nucleic Acids Res 20:3279–3285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Leypoldt F, Titulaer MJ, Aguilar E, Walther J, Bonstrup M, Havemeister S, Teegen B, Lutgehetmann M, Rosenkranz M, Magnus T, Dalmau J (2013) Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 81:1637–1639

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li L, Victoria JG, Wang C, Jones M, Fellers GM, Kunz TH, Delwart E (2010) Bat guano virome: predominance of dietary viruses from insects and plants plus novel mammalian viruses. J Virol 84:6955–6965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu H, Fu Y, Xie J, Cheng J, Ghabrial SA, Li G, Peng Y, Yi X, Jiang D (2011) Widespread endogenization of densoviruses and parvoviruses in animal and human genomes. J Virol 85:9863–9876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu K, Li Y, Jousset FX, Zadori Z, Szelei J, Yu Q, Pham HT, Lepine F, Bergoin M, Tijssen P (2011) The Acheta domesticus densovirus, isolated from the European house cricket, has evolved an expression strategy unique among parvoviruses. J Virol 85:10069–10078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ng TF, Willner DL, Lim YW, Schmieder R, Chau B, Nilsson C, Anthony S, Ruan Y, Rohwer F, Breitbart M (2011) Broad surveys of DNA viral diversity obtained through viral metagenomics of mosquitoes. PloS One 6:e20579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Oh J, Byrd AL, Park M, Kong HH, Segre JA (2016) Temporal stability of the human skin microbiome. Cell 165:854–866

    Article  CAS  PubMed  Google Scholar 

  19. Phan TG, Kapusinszky B, Wang C, Rose RK, Lipton HL, Delwart EL (2011) The fecal viral flora of wild rodents. PLoS Pathog 7:e1002218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Phan TG, Mori D, Deng X, Rajidrajith S, Ranawaka U, Fan Ng TF, Bucardo-Rivera F, Orlandi P, Ahmed K, Delwart E (2015) Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage. Virology 482:98–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shi C, Liu Y, Hu X, Xiong J, Zhang B, Yuan Z (2015) A metagenomic survey of viral abundance and diversity in mosquitoes from Hubei province. PloS One 10:e0129845

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sivaram A, Barde PV, Kumar SR, Yadav P, Gokhale MD, Basu A, Mourya DT (2009) Isolation and characterization of densonucleosis virus from Aedes aegypti mosquitoes and its distribution in India. Intervirology 52:1–7

    Article  CAS  PubMed  Google Scholar 

  23. Suzuki Y, Barik TK, Johnson RM, Rasgon JL (2015) In vitro and in vivo host range of Anopheles gambiae densovirus (AgDNV). Sci Rep 5:12701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Venkatesan A, Benavides DR (2015) Autoimmune encephalitis and its relation to infection. Curr Neurol Neurosci Rep 15:3

    Article  PubMed  Google Scholar 

  26. Walker JE, Saraste M, Runswick MJ, Gay NJ (1982) Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945–951

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang J, Zhang J, Jiang H, Liu C, Yi F, Hu Y (2005) Nucleotide sequence and genomic organization of a newly isolated densovirus infecting Dendrolimus punctatus. J Gen Virol 86:2169–2173

    Article  CAS  PubMed  Google Scholar 

  28. Wang M, Marin A (2006) Characterization and prediction of alternative splice sites. Gene 366:219–227

    Article  CAS  PubMed  Google Scholar 

  29. Wickstrom R, Fowler A, Cooray G, Karlsson-Parra A, Grillner P (2014) Viral triggering of anti-NMDA receptor encephalitis in a child—an important cause for disease relapse. Eur J Paediatr Neurol 18:543–546

    Article  PubMed  Google Scholar 

  30. Woo PC, Lau SK, Teng JL, Tsang AK, Joseph M, Wong EY, Tang Y, Sivakumar S, Bai R, Wernery R, Wernery U, Yuen KY (2014) Metagenomic analysis of viromes of dromedary camel fecal samples reveals large number and high diversity of circoviruses and picobirnaviruses. Virology 471–473:117–125

    Article  PubMed  Google Scholar 

  31. Xu P, Cheng P, Liu Z, Li Y, Murphy RW, Wu K (2012) Complete genome sequence of a monosense densovirus infecting the cotton bollworm, Helicoverpa armigera. J Virol 86:10909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu Q, Tijssen P (2014) Iteradensovirus from the Monarch Butterfly. Danaus plexippus plexippus, Genome announcements 2

    Google Scholar 

  33. Zhou C, Zhang S, Gong Q, Hao A (2015) A novel gemycircularvirus in an unexplained case of child encephalitis. Virol J 12:197

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We acknowledge NHLBI Grant R01 HL105770 to E.L.D, the Blood Systems Research Institute, and NIH/NCATS Colorado CTSA Grant Number UL1 TR001082 for support. The contents are the authors’ sole responsibility and do not necessarily represent official NIH views.

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Authors and Affiliations

  1. Blood Systems Research Institute, San Francisco, CA, 94118, USA

    Tung Gia Phan, Antonio Charlys da Costa, Xutao Deng & Eric Delwart

  2. Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA, 94118, USA

    Tung Gia Phan & Eric Delwart

  3. Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, CO, USA

    Kevin Messacar & Samuel R. Dominguez

  4. Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil

    Antonio Charlys da Costa

Authors
  1. Tung Gia Phan
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  2. Kevin Messacar
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  4. Antonio Charlys da Costa
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  5. Xutao Deng
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  6. Eric Delwart
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Corresponding author

Correspondence to Eric Delwart.

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Funding

This study was funded by NHLBI Grant R01 HL105770 and NIH/NCATS Colorado CTSA Grant Number UL1 TR001082.

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All authors declare that there is no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Phan, T.G., Messacar, K., Dominguez, S.R. et al. A new densovirus in cerebrospinal fluid from a case of anti-NMDA-receptor encephalitis. Arch Virol 161, 3231–3235 (2016). https://doi.org/10.1007/s00705-016-3002-9

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  • DOI: https://doi.org/10.1007/s00705-016-3002-9

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