Skip to main content
SpringerLink
Log in

Reverse Genetics of Filoviruses

  • Chapter
  • First Online:
Marburg- and Ebolaviruses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 411))

Abstract

Reverse genetics systems are used for the generation of recombinant viruses. For filoviruses, this technology has been available for more than 15 years and has been used to investigate questions regarding the molecular biology, pathogenicity, and host adaptation determinants of these viruses. Further, reporter-expressing, recombinant viruses are increasingly used as tools for screening for and characterization of candidate medical countermeasures. Thus, reverse genetics systems represent powerful research tools. Here we provide an overview of available reverse genetics systems for the generation of recombinant filoviruses, potential applications, and the achievements that have been made using these systems.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Albariño CG, Uebelhoer LS, Vincent JP, Khristova ML, Chakrabarti AK, McElroy A, Nichol ST, Towner JS (2013) Development of a reverse genetics system to generate recombinant Marburg virus derived from a bat isolate. Virology 446(1–2):230–237. doi:10.1016/j.virol.2013.07.038

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Albariño CG, Wiggleton Guerrero L, Lo MK, Nichol ST, Towner JS (2015a) Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein. Virology 484:259–264. doi:10.1016/j.virol.2015.06.013

    Article  PubMed  CAS  Google Scholar 

  • Albariño CG, Wiggleton Guerrero L, Spengler JR, Uebelhoer LS, Chakrabarti AK, Nichol ST, Towner JS (2015b) Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of host immune responses. Virology 476:85–91. doi:10.1016/j.virol.2014.12.002

    Article  PubMed  CAS  Google Scholar 

  • Albariño CG, Guerrero LW, Chakrabarti AK, Kainulainen MH, Whitmer SLM, Welch SR, Nichol ST (2016) Virus fitness differences observed between two naturally occurring isolates of Ebola virus Makona variant using a reverse genetics approach. Virology 496:237–243. doi:10.1016/j.virol.2016.06.011

    Article  PubMed  CAS  Google Scholar 

  • Albariño CG, Wiggleton Guerrero L, Jenks HM, Chakrabarti AK, Ksiazek TG, Rollin PE, Nichol ST (2017) Insights into Reston virus spillovers and adaption from virus whole genome sequences. PLoS ONE 12(5):e0178224. doi:10.1371/journal.pone.0178224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bamberg S, Kolesnikova L, Möller P, Klenk H-D, Becker S (2005) VP24 of Marburg virus influences formation of infectious particles. J Virol 79(21):13421–13433. doi:10.1128/JVI.79.21.13421-13433.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker S, Rinne C, Hofsäss U, Klenk H-D, Mühlberger E (1998) Interactions of Marburg virus nucleocapsid proteins. Virology 249(2):406–417. doi:10.1006/viro.1998.9328

    Article  CAS  PubMed  Google Scholar 

  • Beniac DR, Melito PL, Devarennes SL, Hiebert SL, Rabb MJ, Lamboo LL, Jones SM, Booth TF (2012) The organisation of Ebola virus reveals a capacity for extensive, modular polyploidy. PLoS ONE 7(1):e29608. doi:10.1371/journal.pone.0029608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berg JS, Cheney RE (2002) Myosin-X is an unconventional myosin that undergoes intrafilopodial motility. Nat Cell Biol 4(3):246–250. doi:10.1038/ncb762

    Article  CAS  PubMed  Google Scholar 

  • Bharat TA, Riches JD, Kolesnikova L, Welsch S, Krähling V, Davey N, Parsy M-L, Becker S, Briggs JA (2011) Cryo-electron tomography of Marburg virus particles and their morphogenesis within infected cells. PLoS Biol 9(11):e1001196. doi:10.1371/journal.pbio.1001196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bharat TA, Noda T, Riches JD, Kraehling V, Kolesnikova L, Becker S, Kawaoka Y, Briggs JAG (2012) Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. Proc Natl Acad Sci U S A 109(11):4275–4280. doi:10.1073/pnas.1120453109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhattacharyya S, Mulherkar N, Chandran K (2012) Endocytic pathways involved in filovirus entry: advances, implications and future directions. Viruses 4(12):3647–3664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biedenkopf N, Lier C, Becker S (2016) Dynamic phosphorylation of VP30 is essential for Ebola virus life cycle. J Virol 90(10):4914–4925. doi:10.1128/JVI.03257-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bieniasz PD (2006) Late budding domains and host proteins in enveloped virus release. Virology 344(1):55–63. doi:10.1016/j.virol.2005.09.044

    Article  CAS  PubMed  Google Scholar 

  • Brauburger K, Hume AJ, Mühlberger E, Olejnik J (2012) Forty-five years of Marburg virus research. Viruses 4(10):1878–1927. doi:10.3390/v4101878

    Article  PubMed  PubMed Central  Google Scholar 

  • Brauburger K, Deflubé LR, Mühlberger E (2015) Filovirus transcription and replication. Biology and pathogenesis of rhabdo- and filoviruses. World Scientific Publishing, Singapore

    Google Scholar 

  • Bukreyev A, Volchkov VE, Blinov VM, Netesov SV (1993) The GP-protein of Marburg virus contains the region similar to the ‘immunosuppressive domain’ of oncogenic retrovirus P15E proteins. FEBS Lett 323(1–2):183–187

    Article  CAS  PubMed  Google Scholar 

  • Bukreyev AA, Belanov EF, Blinov VM, Netesov SV (1995) Complete nucleotide sequences of Marburg virus genes 5 and 6 encoding VP30 and VP24 proteins. Biochem Mol Biol Int 35(3):605–613

    CAS  PubMed  Google Scholar 

  • Carroll SA, Towner JS, Sealy TK, McMullan LK, Khristova ML, Burt FJ, Swanepoel R, Rollin PE, Nichol ST (2013) Molecular evolution of viruses of the family Filoviridae based on 97 whole-genome sequences. J Virol 87(5):2608–2616. doi:10.1128/JVI.03118-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conzelmann KK (2004) Reverse genetics of Mononegavirales. Curr Top Microbiol Immunol 283:1–41

    CAS  PubMed  Google Scholar 

  • Dietzel E, Schudt G, Krähling V, Matrosovich M, Becker S (2017) Functional characterization of adaptive mutations during the West African Ebola virus outbreak. J Virol 91(2):e01913–e01916. doi:10.1128/JVI.01913-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dolnik O, Kolesnikova L, Stevermann L, Becker S (2010) Tsg101 is recruited by a late domain of the nucleocapsid protein to support budding of Marburg virus-like particles. J Virol 84(15):7847–7856. doi:10.1128/JVI.00476-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dolnik O, Kolesnikova L, Welsch S, Strecker T, Schudt G, Becker S (2014) Interaction with Tsg101 is necessary for the efficient transport and release of nucleocapsids in Marburg virus-infected cells. PLoS Pathog 10(10):e1004463. doi:10.1371/journal.ppat.1004463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dolnik O, Stevermann L, Kolesnikova L, Becker S (2015a) Marburg virus inclusions: a virus-induced microcompartment and interface to multivesicular bodies and the late endosomal compartment. Eur J Cell Biol 94(7–9):323–331. doi:10.1016/j.ejcb.2015.05.006

    Article  CAS  PubMed  Google Scholar 

  • Dolnik O, Volchkova VA, Escudero-Perez B, Lawrence P, Klenk H-D, Volchkov VE (2015b) Shedding of Ebola virus surface glycoprotein is a mechanism of self-regulation of cellular cytotoxicity and has a direct effect on virus infectivity. J Infect Dis 212(Suppl 2):S322–S328. doi:10.1093/infdis/jiv268

    Article  PubMed  Google Scholar 

  • 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. doi:10.1371/journal.ppat.0020073

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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. doi:10.1086/520590

    Article  CAS  PubMed  Google Scholar 

  • Enterlein S, Volchkov V, Weik M, Kolesnikova L, Volchkova V, Klenk H-D, Mühlberger E (2006) Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid protein VP30. J Virol 80(2):1038–1043. doi:10.1128/JVI.80.2.1038-1043.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Enterlein S, Schmidt KM, Schümann M, Conrad D, Krähling V, Olejnik J, Mühlberger E (2009) The Marburg virus 3’ noncoding region structurally and functionally differs from that of Ebola virus. J Virol 83(9):4508–4519. doi:10.1128/JVI.02429-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feldmann H, Will C, Schikore M, Slenczka W, Klenk H-D (1991) Glycosylation and oligomerization of the spike protein of Marburg virus. Virology 182(1):353–356

    Article  CAS  PubMed  Google Scholar 

  • Feldmann H, Mühlberger E, Randolf A, Will C, Kiley MP, Sanchez A, Klenk H-D (1992) Marburg virus, a filovirus: messenger RNAs, gene order, and regulatory elements of the replication cycle. Virus Res 24(1):1–19

    Article  CAS  PubMed  Google Scholar 

  • Feldmann H, Nichol ST, Klenk H-D, Peters CJ, Sanchez A (1994) Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein. Virology 199(2):469–473. doi:10.1006/viro.1994.1147

    Article  CAS  PubMed  Google Scholar 

  • Formenty P, Hatz C, Le Guenno B, Stoll A, Rogenmoser P, Widmer A (1999) Human infection due to Ebola virus, subtype Cote d’Ivoire: clinical and biologic presentation. J Infect Dis 179(Suppl 1):S48–S53. doi:10.1086/514285

    Article  PubMed  Google Scholar 

  • Fowler T, Bamberg S, Möller P, Klenk H-D, Meyer TF, Becker S, Rudel T (2005) Inhibition of Marburg virus protein expression and viral release by RNA interference. J Gen Virol 86(Pt 4):1181–1188. doi:10.1099/vir.0.80622-0

    Article  CAS  PubMed  Google Scholar 

  • Griffiths AJH, Miller JH, Suzuki DT, Lewontin RC, Gelbart WM (2000) An introduction to genetic analysis, Reverse Genetics, 7th edn. W. H. Freeman, New York

    Google Scholar 

  • Groseth A (2017) Generation of recombinant Ebola viruses using reverse genetics. Methods Mol Biol 1628:177–188. doi:10.1007/978-1-4939-7116-9_13

    Article  PubMed  Google Scholar 

  • 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. doi:10.1371/journal.ppat.1002847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartman AL, Bird BH, Towner JS, Antoniadou Z-A, Zaki SR, Nichol ST (2008a) Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of Ebola virus. J Virol 82(6):2699–2704. doi:10.1128/JVI.02344-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartman AL, Ling L, Nichol ST, Hibberd ML (2008b) Whole-genome expression profiling reveals that inhibition of host innate immune response pathways by Ebola virus can be reversed by a single amino acid change in the VP35 protein. J Virol 82(11):5348–5358. doi:10.1128/JVI.00215-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoenen T, Feldmann H (2017) Reverse genetics systems for filoviruses. Methods Mol Biol 1602:159–170. doi:10.1007/978-1-4939-6964-7_11

    Article  PubMed  Google Scholar 

  • Hoenen T, Volchkov V, Kolesnikova L, Mittler E, Timmins J, Ottmann M, Reynard O, Becker S, Weissenhorn W (2005) VP40 octamers are essential for Ebola virus replication. J Virol 79(3):1898–1905. doi:10.1128/JVI.79.3.1898-1905.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoenen T, Groseth A, de Kok-Mercado F, Kuhn JH, Wahl-Jensen V (2011) Minigenomes, transcription and replication competent virus-like particles and beyond: reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses. Antiviral Res 91(2):195–208. doi:10.1016/j.antiviral.2011.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1128/JVI.01525-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoenen T, Groseth A, Callison J, Takada A, Feldmann H (2013) A novel Ebola virus expressing luciferase allows for rapid and quantitative testing of antivirals. Antiviral Res 99(3):207–213. doi:10.1016/j.antiviral.2013.05.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoenen T, Marzi A, Scott DP, Feldmann F, Callison J, Safronetz D, Ebihara H, Feldmann H (2015) Soluble glycoprotein is not required for Ebola virus virulence in guinea pigs. J Infect Dis 212(Suppl 2):S242–S246. doi:10.1093/infdis/jiv111

    Article  PubMed  PubMed Central  Google Scholar 

  • Ilinykh PA, Shen X, Flyak AI, Kuzmina N, Ksiazek TG, Crowe JE Jr, Bukreyev A (2016) Chimeric filoviruses for identification and characterization of monoclonal antibodies. J Virol 90(8):3890–3901. doi:10.1128/JVI.00101-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeffers SA, Sanders DA, Sanchez A (2002) Covalent modifications of the Ebola virus glycoprotein. J Virol 76(24):12463–12472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johansen LM, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehar J, Hensley LE, White JM, Olinger GG (2013) FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Sci Transl Med 5(190):190ra179. doi:10.1126/scitranslmed.3005471

  • Koehler A, Kolesnikova L, Welzel U, Schudt G, Herwig A, Becker S (2015) A single amino acid change in the Marburg virus matrix protein VP40 provides a replicative advantage in a species-specific manner. J Virol 90(3):1444–1454. doi:10.1128/JVI.02670-15

    Article  PubMed  CAS  Google Scholar 

  • Kolesnikova L, Mühlberger E, Ryabchikova E, Becker S (2000) Ultrastructural organization of recombinant Marburg virus nucleoprotein: comparison with Marburg virus inclusions. J Virol 74(8):3899–3904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kolesnikova L, Bohil AB, Cheney RE, Becker S (2007) Budding of Marburgvirus is associated with filopodia. Cell Microbiol 9(4):939–951. doi:10.1111/j.1462-5822.2006.00842.x

    Article  CAS  PubMed  Google Scholar 

  • Kolesnikova L, Mittler E, Schudt G, Shams-Eldin H, Becker S (2012) Phosphorylation of Marburg virus matrix protein VP40 triggers assembly of nucleocapsids with the viral envelope at the plasma membrane. Cell Microbiol 14(2):182–197. doi:10.1111/j.1462-5822.2011.01709.x

    Article  CAS  PubMed  Google Scholar 

  • Krähling V, Dolnik O, Kolesnikova L, Schmidt-Chanasit J, Jordan I, Sandig V, Günther S, Becker S (2010) Establishment of fruit bat cells (Rousettus aegyptiacus) as a model system for the investigation of filoviral infection. PLoS Negl Trop Dis 4(8):e802. doi:10.1371/journal.pntd.0000802

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kuhn JH (2015) Ebolavirus and marburgvirus infections. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J (eds) Harrison’s principles of internal medicine, vol 2, 19th edn. McGraw-Hill Education, Columbus, USA, pp 1323–1329

    Google Scholar 

  • Kuhn JH (2017) Guide to the correct use of filoviral nomenclature. Curr Top Microbiol Immunol. doi:10.1007/82_2017_7

    Google Scholar 

  • Kuhn JH, Bao Y, Bavari S, Becker S, Bradfute S, Brister JR, Bukreyev AA, Chandran K, Davey RA, Dolnik O, Dye JM, Enterlein S, Hensley LE, Honko AN, Jahrling PB, Johnson KM, Kobinger G, Leroy EM, Lever MS, Mühlberger E, Netesov SV, Olinger GG, Palacios G, Patterson JL, Paweska JT, Pitt L, Radoshitzky SR, Saphire EO, Smither SJ, Swanepoel R, Towner JS, van der Groen G, Volchkov VE, Wahl-Jensen V, Warren TK, Weidmann M, Nichol ST (2013) Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae. Arch Virol 158(1):301–311. doi:10.1007/s00705-012-1454-0

    Article  CAS  PubMed  Google Scholar 

  • Kuhn JH, Andersen KG, Bào Y, Bavari S, Becker S, Bennett RS, Bergman NH, Blinkova O, Bradfute S, Brister JR, Bukreyev A, Chandran K, Chepurnov AA, Davey RA, Dietzgen RG, Doggett NA, Dolnik O, Dye JM, Enterlein S, Fenimore PW, Formenty P, Freiberg AN, Garry RF, Garza NL, Gire SK, Gonzalez J-P, Griffiths A, Happi CT, Hensley LE, Herbert AS, Hevey MC, Hoenen T, Honko AN, Ignatyev GM, Jahrling PB, Johnson JC, Johnson KM, Kindrachuk J, Klenk H-D, Kobinger G, Kochel TJ, Lackemeyer MG, Lackner DF, Leroy EM, Lever MS, Mühlberger E, Netesov SV, Olinger GG, Omilabu SA, Palacios G, Panchal RG, Park DJ, Patterson JL, Paweska JT, Peters CJ, Pettitt J, Pitt L, Radoshitzky SR, Ryabchikova EI, Saphire EO, Sabeti PC, Sealfon R, Shestopalov AM, Smither SJ, Sullivan NJ, Swanepoel R, Takada A, Towner JS, van der Groen G, Volchkov VE, Volchkova VA, Wahl-Jensen V, Warren TK, Warfield KL, Weidmann M, Nichol ST (2014) Filovirus RefSeq entries: evaluation and selection of filovirus type variants, type sequences, and names. Viruses 6(9):3663–3682. doi:10.3390/v6093663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Guenno B, Formenty P, Boesch C (1999) Ebola virus outbreaks in the Ivory Coast and Liberia, 1994–1995. Curr Top Microbiol Immunol 235:77–84

    PubMed  Google Scholar 

  • Lofts LL, Ibrahim MS, Negley DL, Hevey MC, Schmaljohn AL (2007) Genomic differences between guinea pig lethal and nonlethal Marburg virus variants. J Infect Dis 196(Suppl 2):S305–S312. doi:10.1086/520585

    Article  CAS  PubMed  Google Scholar 

  • Madrid PB, Chopra S, Manger ID, Gilfillan L, Keepers TR, Shurtleff AC, Green CE, Iyer LV, Dilks HH, Davey RA, Kolokoltsov AA, Carrion R Jr, Patterson JL, Bavari S, Panchal RG, Warren TK, Wells JB, Moos WH, Burke RL, Tanga MJ (2013) A systematic screen of FDA-approved drugs for inhibitors of biological threat agents. PLoS ONE 8(4):e60579. doi:10.1371/journal.pone.0060579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin B, Canard B, Decroly E (2017) Filovirus proteins for antiviral drug discovery: structure/function bases of the replication cycle. Antiviral Res 141:48–61. doi:10.1016/j.antiviral.2017.02.004

    Article  CAS  PubMed  Google Scholar 

  • Martinez MJ, Volchkova VA, Raoul H, Alazard-Dany N, Reynard O, Volchkov VE (2011) Role of VP30 phosphorylation in the Ebola virus replication cycle. J Infect Dis 204(Suppl 3):S934–S940. doi:10.1093/infdis/jir320

    Article  CAS  PubMed  Google Scholar 

  • Martínez MJ, Biedenkopf N, Volchkova V, Hartlieb B, Alazard-Dany N, Reynard O, Becker S, Volchkov V (2008) Role of Ebola virus VP30 in transcription reinitiation. J Virol 82(24):12569–12573. doi:10.1128/JVI.01395-08

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mateo M, Carbonnelle C, Reynard O, Kolesnikova L, Nemirov K, Page A, Volchkova VA, Volchkov VE (2011) VP24 is a molecular determinant of Ebola virus virulence in guinea pigs. J Infect Dis 204(Suppl 3):S1011–S1020. doi:10.1093/infdis/jir338

    Article  CAS  PubMed  Google Scholar 

  • Mavrakis M, Kolesnikova L, Schoehn G, Becker S, Ruigrok RWH (2002) Morphology of Marburg virus NP-RNA. Virology 296(2):300–307. doi:10.1006/viro.2002.1433

    Article  CAS  PubMed  Google Scholar 

  • Mehedi M, Falzarano D, Seebach J, Hu X, Carpenter MS, Schnittler H-J, Feldmann H (2011) A new Ebola virus nonstructural glycoprotein expressed through RNA editing. J Virol 85(11):5406–5414. doi:10.1128/JVI.02190-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehedi M, Hoenen T, Robertson S, Ricklefs S, Dolan MA, Taylor T, Falzarano D, Ebihara H, Porcella SF, Feldmann H (2013) Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. PLoS Pathog 9(10):e1003677. doi:10.1371/journal.ppat.1003677

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Miller EH, Chandran K (2012) Filovirus entry into cells—new insights. Curr Opin Virol 2(2):206–214. doi:10.1016/j.coviro.2012.02.015

    Article  CAS  PubMed  Google Scholar 

  • Miranda ME, Miranda NL (2011) Reston ebolavirus in humans and animals in the Philippines: a review. J Infect Dis 204(Suppl 3):S757–S760. doi:10.1093/infdis/jir296

    Article  PubMed  Google Scholar 

  • Miranda ME, Ksiazek TG, Retuya TJ, Khan AS, Sanchez A, Fulhorst CF, Rollin PE, Calaor AB, Manalo DL, Roces MC, Dayrit MM, Peters CJ (1999) Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996. J Infect Dis 179(Suppl 1):S115–S119. doi:10.1086/514314

    Article  PubMed  Google Scholar 

  • Mittler E, Kolesnikova L, Herwig A, Dolnik O, Becker S (2013) Assembly of the Marburg virus envelope. Cell Microbiol 15(2):270–284. doi:10.1111/cmi.12076

    Article  CAS  PubMed  Google Scholar 

  • Möller P, Pariente N, Klenk H-D, Becker S (2005) Homo-oligomerization of Marburgvirus VP35 is essential for its function in replication and transcription. J Virol 79(23):14876–14886. doi:10.1128/JVI.79.23.14876-14886.2005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mpanju OM, Towner JS, Dover JE, Nichol ST, Wilson CA (2006) Identification of two amino acid residues on Ebola virus glycoprotein 1 critical for cell entry. Virus Res 121(2):205–214. doi:10.1016/j.virusres.2006.06.002

    Article  CAS  PubMed  Google Scholar 

  • Mühlberger E (2007) Filovirus replication and transcription. Future Virol 2(2):205–215. doi:10.2217/17460794.2.2.205

    Article  PubMed  PubMed Central  Google Scholar 

  • Mühlberger E, Trommer S, Funke C, Volchkov V, Klenk H-D, Becker S (1996) Termini of all mRNA species of Marburg virus: sequence and secondary structure. Virology 223(2):376–380. doi:10.1006/viro.1996.0490

    Article  PubMed  Google Scholar 

  • Mühlberger E, Lötfering B, Klenk H-D, Becker S (1998) Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are sufficient to mediate replication and transcription of Marburg virus-specific monocistronic minigenomes. J Virol 72(11):8756–8764

    PubMed  PubMed Central  Google Scholar 

  • Mühlberger E, Weik M, Volchkov VE, Klenk H-D, 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

    PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neumann G, Ebihara H, Takada A, Noda T, Kobasa D, Jasenosky LD, Watanabe S, Kim JH, Feldmann H, Kawaoka Y (2005) Ebola virus VP40 late domains are not essential for viral replication in cell culture. J Virol 79(16):10300–10307. doi:10.1128/JVI.79.16.10300-10307.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1128/JVI.02486-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panchal RG, Kota KP, Spurgers KB, Ruthel G, Tran JP, Boltz RC, Bavari S (2010) Development of high-content imaging assays for lethal viral pathogens. J Biomol Screen 15(7):755–765. doi:10.1177/1087057110374357

    Article  CAS  PubMed  Google Scholar 

  • Panchal RG, Reid SP, Tran JP, Bergeron AA, Wells J, Kota KP, Aman J, Bavari S (2012) Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. Antiviral Res 93(1):23–29. doi:10.1016/j.antiviral.2011.10.011

    Article  CAS  PubMed  Google Scholar 

  • Prins KC, Delpeut S, Leung DW, Reynard O, Volchkova VA, Reid SP, Ramanan P, Cárdenas 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. doi:10.1128/JVI.02459-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Racaniello VR, Baltimore D (1981) Cloned poliovirus complementary DNA is infectious in mammalian cells. Science 214(4523):916–919

    Article  CAS  PubMed  Google Scholar 

  • Radoshitzky SR, Warfield KL, Chi X, Dong L, Kota K, Bradfute SB, Gearhart JD, Retterer C, Kranzusch PJ, Misasi JN, Hogenbirk MA, Wahl-Jensen V, Volchkov VE, Cunningham JM, Jahrling PB, Aman MJ, Bavari S, Farzan M, Kuhn JH (2011) Ebolavirus Δ-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry. J Virol 85(17):8502–8513. doi:10.1128/JVI.02600-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez A, Kiley MP, Holloway BP, Auperin DD (1993) Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Res 29(3):215–240

    Article  CAS  PubMed  Google Scholar 

  • Sanchez A, Trappier SG, Mahy BWJ, Peters CJ, Nichol ST (1996) The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A 93(8):3602–3607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt KM, Mühlberger E (2016) Marburg virus reverse genetics systems. Viruses 8(6):178. doi:10.3390/v8060178

    Article  PubMed Central  CAS  Google Scholar 

  • Schmidt KM, Schümann M, Olejnik J, Krähling V, Mühlberger E (2011) Recombinant Marburg virus expressing eGFP allows rapid screening of virus growth and real-time visualization of virus spread. J Infect Dis 204(Suppl 3):S861–S870. doi:10.1093/infdis/jir308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schnell MJ, Mebatsion T, Conzelmann K-K (1994) Infectious rabies viruses from cloned cDNA. EMBO J 13(18):4195–4203

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1073/pnas.1307681110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slagsvold T, Pattni K, Malerød L, Stenmark H (2006) Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol 16(6):317–326. doi:10.1016/j.tcb.2006.04.004

    Article  CAS  PubMed  Google Scholar 

  • Towner JS, Paragas J, Dover JE, Gupta M, Goldsmith CS, Huggins JW, Nichol ST (2005) Generation of eGFP expressing recombinant Zaire Ebola virus for analysis of early pathogenesis events and high-throughput antiviral drug screening. Virology 332(1):20–27. doi:10.1016/j.virol.2004.10.048

    Article  CAS  PubMed  Google Scholar 

  • Towner JS, Khristova ML, Sealy TK, Vincent MJ, Erickson BR, Bawiec DA, Hartman AL, Comer JA, Zaki SR, Ströher U, Gomes da Silva F, del Castillo F, Rollin PE, Ksiazek TG, Nichol ST (2006) Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola. J Virol 80(13):6497–6516. doi:10.1128/JVI.00069-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Towner JS, Amman BR, Sealy TK, Carroll SA, Comer JA, Kemp A, Swanepoel R, Paddock CD, Balinandi S, Khristova ML, Formenty PBH, Albarino CG, Miller DM, Reed ZD, Kayiwa JT, Mills JN, Cannon DL, Greer PW, Byaruhanga E, Farnon EC, Atimnedi P, Okware S, Katongole-Mbidde E, Downing R, Tappero JW, Zaki SR, Ksiazek TG, Nichol ST, Rollin PE (2009) Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog 5(7):e1000536. doi:10.1371/journal.ppat.1000536

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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 212(Suppl 2):S129–S137. doi:10.1093/infdis/jiu681

    Article  PubMed  PubMed Central  Google Scholar 

  • Volchkov VE, Becker S, Volchkova VA, Ternovoj VA, Kotov AN, Netesov SV, Klenk H-D (1995) GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology 214(2):421–430

    Article  CAS  PubMed  Google Scholar 

  • Volchkov VE, Feldmann H, Volchkova VA, Klenk H-D (1998) Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc Natl Acad Sci U S A 95(10):5762–5767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volchkov VE, Volchkova VA, Chepurnov AA, Blinov VM, Dolnik O, Netesov SV, Feldmann H (1999) Characterization of the L gene and 5′ trailer region of Ebola virus. J Gen Virol 80(Pt 2):355–362. doi:10.1099/0022-1317-80-2-355

    Article  CAS  PubMed  Google Scholar 

  • Volchkov VE, Volchkova VA, Mühlberger E, Kolesnikova LV, Weik M, Dolnik O, Klenk H-D (2001) Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 291(5510):1965–1969. doi:10.1126/science.1057269

    Article  CAS  PubMed  Google Scholar 

  • Volchkova VA, Klenk H-D, Volchkov VE (1999) Delta-peptide is the carboxy-terminal cleavage fragment of the nonstructural small glycoprotein sGP of Ebola virus. Virology 265(1):164–171. doi:10.1006/viro.1999.0034

    Article  CAS  PubMed  Google Scholar 

  • Volchkova VA, Dolnik O, Martinez MJ, Reynard O, Volchkov VE (2015) RNA editing of the GP gene of Ebola virus is an important pathogenicity factor. J Infect Dis 212(Suppl 2):S226–S233. doi:10.1093/infdis/jiv309

    Article  PubMed  Google Scholar 

  • Warren TK, Warfield KL, Wells J, Enterlein S, Smith M, Ruthel G, Yunus AS, Kinch MS, Goldblatt M, Aman MJ, Bavari S (2010) Antiviral activity of a small-molecule inhibitor of filovirus infection. Antimicrob Agents Chemother 54(5):2152–2159. doi:10.1128/AAC.01315-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1128/JVI.01272-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Welch SR, Guerrero LW, Chakrabarti AK, McMullan LK, Flint M, Bluemling GR, Painter GR, Nichol ST, Spiropoulou CF, Albariño CG (2016) Lassa and Ebola virus inhibitors identified using minigenome and recombinant virus reporter systems. Antiviral Res 136:9–18. doi:10.1016/j.antiviral.2016.10.007

    Article  CAS  PubMed  Google Scholar 

  • Welsch S, Kolesnikova L, Krähling V, Riches JD, Becker S, Briggs JA (2010) Electron tomography reveals the steps in filovirus budding. PLoS Pathog 6(4):e1000875. doi:10.1371/journal.ppat.1000875

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wenigenrath J, Kolesnikova L, Hoenen T, Mittler E, Becker S (2010) Establishment and application of an infectious virus-like particle system for Marburg virus. J Gen Virol 91(Pt 5):1325–1334. doi:10.1099/vir.0.018226-0

    Article  CAS  PubMed  Google Scholar 

  • Wijesinghe KJ, Stahelin RV (2015) Investigation of the lipid binding properties of the Marburg virus matrix protein VP40. J Virol 90(6):3074–3085. doi:10.1128/JVI.02607-15

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Laura Bollinger and Jiro Wada (IRF-Frederick) for critically editing this chapter and for figure preparation, respectively.

Disclaimer: The views and conclusions contained in this document are those of the author and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the US Department of Health and Human Services or of the institutions and companies affiliated with the author. This work was supported in part through Battelle Memorial Institute’s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016I. Subcontractors to Battelle Memorial Institute who performed this work are Y.C., J.H.K., and C.F., employees of Tunnell Government Services, Inc.

Author information

Authors and Affiliations

  1. Friedrich-Loeffler-Institut, Südufer 10, 17493, Greifswald—Insel Riems, Germany

    Thomas Hoenen & Janine Brandt

  2. Integrated Research Facility at Fort Detrick (IRF-Frederick), Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), B-8200 Research Plaza, Fort Detrick, Frederick, MD, 21702, USA

    Yíngyún Caì, Jens H. Kuhn & Courtney Finch

Authors
  1. Thomas Hoenen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janine Brandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yíngyún Caì
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jens H. Kuhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Courtney Finch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Thomas Hoenen or Jens H. Kuhn .

Editor information

Editors and Affiliations

  1. Boston University School of Medicine , Boston, Massachusetts, USA

    Elke Mühlberger

  2. NIAID, National Institutes of Health NIAID, Frederick, Maryland, USA

    Lisa L. Hensley

  3. Centers for Disease Control & Prevention, Atlanta, Georgia, USA

    Jonathan S. Towner

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Hoenen, T., Brandt, J., Caì, Y., Kuhn, J.H., Finch, C. (2017). Reverse Genetics of Filoviruses. In: Mühlberger, E., Hensley, L., Towner, J. (eds) Marburg- and Ebolaviruses. Current Topics in Microbiology and Immunology, vol 411. Springer, Cham. https://doi.org/10.1007/82_2017_55

Download citation

Publish with us

Policies and ethics

Search

Navigation