Reverse Genetics Systems for Filoviruses.

Bianca S Bodmer, Thomas Hoenen
Author Information
  1. Bianca S Bodmer: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
  2. Thomas Hoenen: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany. thomas.hoenen@fli.de.

Abstract

Filoviruses are causative agents of severe hemorrhagic fevers with high case fatality rates in humans. For studies of virus biology and the subsequent development of countermeasures, reverse genetic systems, and especially those facilitating the generation of recombinant filoviruses, are indispensable. Here, we describe the generation of recombinant filoviruses from cDNA.

Keywords

References

  1. Kuhn JH, Amarasinghe GK, Basler CF, Bavari S, Bukreyev A, Chandran K, Crozier I, Dolnik O, Dye JM, Formenty PBH, Griffiths A, Hewson R, Kobinger GP, Leroy EM, Muhlberger E, Netesov SV, Palacios G, Palyi B, Paweska JT, Smither SJ, Takada A, Towner JS, Wahl V, Ictv Report C (2019) ICTV virus taxonomy profile: filoviridae. J Gen Virol 100(6):911–912. https://doi.org/10.1099/jgv.0.001252 [DOI: 10.1099/jgv.0.001252]
  2. Burk R, Bollinger L, Johnson JC, Wada J, Radoshitzky SR, Palacios G, Bavari S, Jahrling PB, Kuhn JH (2016) Neglected filoviruses. FEMS Microbiol Rev 40(4):494–519. https://doi.org/10.1093/femsre/fuw010 [DOI: 10.1093/femsre/fuw010]
  3. Yamaoka S, Ebihara H (2021) Pathogenicity and virulence of Ebolaviruses with species- and variant-specificity. Virulence 12(1):885–901. https://doi.org/10.1080/21505594.2021.1898169 [DOI: 10.1080/21505594.2021.1898169]
  4. History of Ebola Virus Disease (EVD) Outbreaks. CDC. https://www.cdc.gov/vhf/ebola/history/chronology.html . Accessed 30 Mar 2022
  5. WHO (2020) Ebola virus disease Democratic Republic of Congo: external situation report 98/2020. https://www.who.int/publications/i/item/10665-332654 . Accessed 30 Mar 2022
  6. Goldstein T, Anthony SJ, Gbakima A, Bird BH, Bangura J, Tremeau-Bravard A, Belaganahalli MN, Wells HL, Dhanota JK, Liang E, Grodus M, Jangra RK, DeJesus VA, Lasso G, Smith BR, Jambai A, Kamara BO, Kamara S, Bangura W, Monagin C, Shapira S, Johnson CK, Saylors K, Rubin EM, Chandran K, Lipkin WI, Mazet JAK (2018) The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses. Nat Microbiol 3(10):1084–1089. https://doi.org/10.1038/s41564-018-0227-2 [DOI: 10.1038/s41564-018-0227-2]
  7. Negredo A, Palacios G, Vazquez-Moron S, Gonzalez F, Dopazo H, Molero F, Juste J, Quetglas J, Savji N, de la Cruz MM, Herrera JE, Pizarro M, Hutchison SK, Echevarria JE, Lipkin WI, Tenorio A (2011) Discovery of an ebolavirus-like filovirus in europe. PLoS Pathog 7(10):e1002304. https://doi.org/10.1371/journal.ppat.1002304 [DOI: 10.1371/journal.ppat.1002304]
  8. Yang XL, Tan CW, Anderson DE, Jiang RD, Li B, Zhang W, Zhu Y, Lim XF, Zhou P, Liu XL, Guan W, Zhang L, Li SY, Zhang YZ, Wang LF, Shi ZL (2019) Characterization of a filovirus (Mengla virus) from Rousettus bats in China. Nat Microbiol 4(3):390–395. https://doi.org/10.1038/s41564-018-0328-y [DOI: 10.1038/s41564-018-0328-y]
  9. FDA (2020) FDA approves first treatment for Ebola virus. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-ebola-virus . Accessed 30 Mar 2022
  10. FDA (2020) FDA approves treatment for Ebola virus. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-ebola-virus . Accessed 30 Mar 2022
  11. FDA (2019) First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response. https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health . Accessed 30 Mar 2022
  12. EMA (2019) Ervebo. https://www.ema.europa.eu/en/medicines/human/EPAR/ervebo . Accessed 30 Mar 2022
  13. EMA (2020) Zabdeno. https://www.ema.europa.eu/en/medicines/human/EPAR/zabdeno . Accessed 30 Mar 2022
  14. EMA (2020) Mvabea. https://www.ema.europa.eu/en/medicines/human/EPAR/mvabea . Accessed 30 Mar 2022
  15. Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S (1999) Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol 73(3):2333–2342. https://doi.org/10.1128/JVI.73.3.2333-2342.1999 [DOI: 10.1128/JVI.73.3.2333-2342.1999]
  16. Banadyga L, Hoenen T, Ambroggio X, Dunham E, Groseth A, Ebihara H (2017) Ebola virus VP24 interacts with NP to facilitate nucleocapsid assembly and genome packaging. Sci Rep 7(1):7698. https://doi.org/10.1038/s41598-017-08167-8 [DOI: 10.1038/s41598-017-08167-8]
  17. Watt A, Moukambi F, Banadyga L, Groseth A, Callison J, Herwig A, Ebihara H, Feldmann H, Hoenen T (2014) A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity. J Virol 88(18):10511–10524. https://doi.org/10.1128/JVI.01272-14 [DOI: 10.1128/JVI.01272-14]
  18. Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonnelle C, Volchkov VE, Nichol ST, Basler CF (2006) Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol 80(11):5156–5167. https://doi.org/10.1128/JVI.02349-05 [DOI: 10.1128/JVI.02349-05]
  19. Feagins AR, Basler CF (2015) Lloviu virus VP24 and VP35 proteins function as innate immune antagonists in human and bat cells. Virology 485:145–152. https://doi.org/10.1016/j.virol.2015.07.010 [DOI: 10.1016/j.virol.2015.07.010]
  20. He FB, Khan H, Huttunen M, Kolehmainen P, Melen K, Maljanen S, Qu M, Jiang M, Kakkola L, Julkunen I (2021) Filovirus VP24 proteins differentially regulate RIG-I and MDA5-dependent type I and III interferon promoter activation. Front Immunol 12:694105. https://doi.org/10.3389/fimmu.2021.694105 [DOI: 10.3389/fimmu.2021.694105]
  21. Noda T, Sagara H, Suzuki E, Takada A, Kida H, Kawaoka Y (2002) Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP. J Virol 76(10):4855–4865. https://doi.org/10.1128/jvi.76.10.4855-4865.2002 [DOI: 10.1128/jvi.76.10.4855-4865.2002]
  22. Valmas C, Grosch MN, Schumann M, Olejnik J, Martinez O, Best SM, Krahling V, Basler CF, Muhlberger E (2010) Marburg virus evades interferon responses by a mechanism distinct from ebola virus. PLoS Pathog 6(1):e1000721. https://doi.org/10.1371/journal.ppat.1000721 [DOI: 10.1371/journal.ppat.1000721]
  23. Moller-Tank S, Maury W (2015) Ebola virus entry: a curious and complex series of events. PLoS Pathog 11(4):e1004731. https://doi.org/10.1371/journal.ppat.1004731 [DOI: 10.1371/journal.ppat.1004731]
  24. Wendt L, Bostedt L, Hoenen T, Groseth A (2019) High-throughput screening for negative-stranded hemorrhagic fever viruses using reverse genetics. Antivir Res 170:104569. https://doi.org/10.1016/j.antiviral.2019.104569 [DOI: 10.1016/j.antiviral.2019.104569]
  25. Volchkov VE, Volchkova VA, Muhlberger E, Kolesnikova LV, Weik M, Dolnik O, Klenk HD (2001) Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 291(5510):1965–1969. https://doi.org/10.1126/science.1057269 [DOI: 10.1126/science.1057269]
  26. Neumann G, Feldmann H, Watanabe S, Lukashevich I, Kawaoka Y (2002) Reverse genetics demonstrates that proteolytic processing of the Ebola virus glycoprotein is not essential for replication in cell culture. J Virol 76(1):406–410. https://doi.org/10.1128/jvi.76.1.406-410.2002 [DOI: 10.1128/jvi.76.1.406-410.2002]
  27. Hoenen T, Shabman RS, Groseth A, Herwig A, Weber M, Schudt G, Dolnik O, Basler CF, Becker S, Feldmann H (2012) Inclusion bodies are a site of ebolavirus replication. J Virol 86(21):11779–11788. https://doi.org/10.1128/JVI.01525-12 [DOI: 10.1128/JVI.01525-12]
  28. Brandt J, Wendt L, Bodmer BS, Mettenleiter TC, Hoenen T (2020) The cellular protein CAD is recruited into Ebola virus inclusion bodies by the nucleoprotein NP to facilitate genome replication and transcription. Cells 9(5). https://doi.org/10.3390/cells9051126
  29. Wendt L, Brandt J, Bodmer BS, Reiche S, Schmidt ML, Traeger S, Hoenen T (2020) The Ebola virus nucleoprotein recruits the nuclear RNA export factor NXF1 into inclusion bodies to facilitate viral protein expression. Cells 9(1). https://doi.org/10.3390/cells9010187
  30. Groseth A, Marzi A, Hoenen T, Herwig A, Gardner D, Becker S, Ebihara H, Feldmann H (2012) The Ebola virus glycoprotein contributes to but is not sufficient for virulence in vivo. PLoS Pathog 8(8):e1002847. https://doi.org/10.1371/journal.ppat.1002847 [DOI: 10.1371/journal.ppat.1002847]
  31. Prins KC, Delpeut S, Leung DW, Reynard O, Volchkova VA, Reid SP, Ramanan P, Cardenas WB, Amarasinghe GK, Volchkov VE, Basler CF (2010) Mutations abrogating VP35 interaction with double-stranded RNA render Ebola virus avirulent in guinea pigs. J Virol 84(6):3004–3015. https://doi.org/10.1128/JVI.02459-09 [DOI: 10.1128/JVI.02459-09]
  32. Ebihara H, Takada A, Kobasa D, Jones S, Neumann G, Theriault S, Bray M, Feldmann H, Kawaoka Y (2006) Molecular determinants of Ebola virus virulence in mice. PLoS Pathog 2(7):e73. https://doi.org/10.1371/journal.ppat.0020073 [DOI: 10.1371/journal.ppat.0020073]
  33. Neumann G, Geisbert TW, Ebihara H, Geisbert JB, Daddario-DiCaprio KM, Feldmann H, Kawaoka Y (2007) Proteolytic processing of the Ebola virus glycoprotein is not critical for Ebola virus replication in nonhuman primates. J Virol 81(6):2995–2998. https://doi.org/10.1128/JVI.02486-06 [DOI: 10.1128/JVI.02486-06]
  34. Schudt G, Kolesnikova L, Dolnik O, Sodeik B, Becker S (2013) Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances. Proc Natl Acad Sci U S A 110(35):14402–14407. https://doi.org/10.1073/pnas.1307681110 [DOI: 10.1073/pnas.1307681110]
  35. Mittler E, Schudt G, Halwe S, Rohde C, Becker S (2018) A fluorescently labeled Marburg Virus glycoprotein as a new tool to study viral transport and assembly. J Infect Dis 218(suppl_5):S318–S326. https://doi.org/10.1093/infdis/jiy424 [DOI: 10.1093/infdis/jiy424]
  36. Ebihara H, Theriault S, Neumann G, Alimonti JB, Geisbert JB, Hensley LE, Groseth A, Jones SM, Geisbert TW, Kawaoka Y, Feldmann H (2007) In vitro and in vivo characterization of recombinant Ebola viruses expressing enhanced green fluorescent protein. J Infect Dis 196(Suppl 2):S313–S322. https://doi.org/10.1086/520590 [DOI: 10.1086/520590]
  37. Kondratowicz AS, Lennemann NJ, Sinn PL, Davey RA, Hunt CL, Moller-Tank S, Meyerholz DK, Rennert P, Mullins RF, Brindley M, Sandersfeld LM, Quinn K, Weller M, McCray PB Jr, Chiorini J, Maury W (2011) T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus. Proc Natl Acad Sci U S A 108(20):8426–8431. https://doi.org/10.1073/pnas.1019030108 [DOI: 10.1073/pnas.1019030108]
  38. Tsuda Y, Hoenen T, Banadyga L, Weisend C, Ricklefs SM, Porcella SF, Ebihara H (2015) An improved reverse genetics system to overcome cell-type-dependent Ebola virus genome plasticity. J Infect Dis. https://doi.org/10.1093/infdis/jiu681
  39. Hoenen T, Groseth A, Feldmann F, Marzi A, Ebihara H, Kobinger G, Gunther S, Feldmann H (2014) Complete genome sequences of three ebola virus isolates from the 2014 outbreak in west Africa. Genome Announc 2(6):e01331–e01314. https://doi.org/10.1128/genomeA.01331-14 [DOI: 10.1128/genomeA.01331-14]
  40. Volchkova VA, Dolnik O, Martinez MJ, Reynard O, Volchkov VE (2011) Genomic RNA editing and its impact on Ebola virus adaptation during serial passages in cell culture and infection of guinea pigs. J Infect Dis 204(Suppl 3):S941–S946. https://doi.org/10.1093/infdis/jir321 [DOI: 10.1093/infdis/jir321]
  41. Haddock E, Feldmann F, Feldmann H (2016) Effective chemical inactivation of Ebola virus. Emerg Infect Dis 22(7):1292–1294. https://doi.org/10.3201/eid2207.160233 [DOI: 10.3201/eid2207.160233]
  42. Smither SJ, Weller SA, Phelps A, Eastaugh L, Ngugi S, O’Brien LM, Steward J, Lonsdale SG, Lever MS (2015) Buffer AVL alone does not inactivate Ebola virus in a representative clinical sample type. J Clin Microbiol 53(10):3148–3154. https://doi.org/10.1128/JCM.01449-15 [DOI: 10.1128/JCM.01449-15]

MeSH Term

Humans
Filoviridae
Reverse Genetics
DNA, Complementary
Hemorrhagic Fever, Ebola
Ebolavirus

Chemicals

DNA, Complementary

Word Cloud

Created with Highcharts 10.0.0virusFilovirusesgenerationrecombinantfilovirusesReverseclonecausativeagentsseverehemorrhagicfevershighcasefatalityrateshumansstudiesbiologysubsequentdevelopmentcountermeasuresreversegeneticsystemsespeciallyfacilitatingindispensabledescribecDNAGeneticsSystemsEbolaFull-lengthsystemInfectiousMarburgRecombinantgenetics

Similar Articles

Cited By