Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin

English version České info

Crimean Congo hemorrhagic fever (CCHF) is a severe viral disease characterized by rapid-onset fever, hemorrhage, and high case fatality rates. CCHF virus (CCHFV), the causative agent of CCHF, is a negative-strand RNA virus of the family Bunyaviridae (genus Nairovirus). No specific treatments or efficacious vaccines exist to combat CCHF. To investigate molecular determinants of nairovirus pathogenesis and biology, we developed a reverse genetics system capable of generating CCHFV variants with genome sequences defined by the plasmids transfected into cells for virus recovery. Our system is the first to demonstrate that a nairovirus can be efficiently recovered from the simple transfection of plasmid DNA, paving the way for specifically editing genomes of CCHFV and other nairoviruses. Using this system, we engineered mutations blocking the cleavage of CCHFV’s non-structural glycoproteins at a motif recognized by the host protease furin. Using this furin-resistant CCHFV variant, we demonstrate that direct cleavage of the viral glycoprotein by furin results in a lag in virion production, revealing a function of these glycoproteins in efficient CCHFV replication. Our experiments highlight the utility of a reverse genetics system for developing viral variants for investigating CCHFV protein function and for rationally designing vaccine strains.

Vyšlo v časopise: Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004879
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004879

Souhrn

Zdroje

1. Ergonul O (2012) Crimean-Congo hemorrhagic fever virus: new outbreaks, new discoveries. Current Opinion in Virology 2: 215–220. doi: 10.1016/j.coviro.2012.03.001 22482717

2. Estrada-Peña A, Palomar AM, Santibáñez P, Sánchez N, Habela MA, et al. (2012) Crimean-congo hemorrhagic Fever virus in ticks, southwestern europe, 2010. Emerg Infect Dis 18: 179–180. doi: 10.3201/eid1801.111040 22261502

3. Maltezou HC, Andonova L, Andraghetti R, Bouloy M, Ergonul O, et al. (2010) Crimean-Congo hemorrhagic fever in Europe: current situation calls for preparedness. Euro Surveill 15: 19504. 20403306

4. Ergonul O (2006) Crimean-Congo haemorrhagic fever. Lancet Infect Dis 6: 203–214. doi: 10.1016/S1473-3099(06)70435-2 16554245

5. Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Hughes JM (2002) Public health assessment of potential biological terrorism agents. Emerg Infect Dis 8: 225–230. 11897082

6. Altamura LA, Bertolotti-Ciarlet A, Teigler J, Paragas J, Schmaljohn CS, et al. (2007) Identification of a novel C-terminal cleavage of Crimean-Congo hemorrhagic fever virus PreGN that leads to generation of an NSM protein. J Virol 81: 6632–6642. doi: 10.1128/JVI.02730-06 17409136

7. Sanchez AJ, Vincent MJ, Nichol ST (2002) Characterization of the glycoproteins of Crimean-Congo hemorrhagic fever virus. J Virol 76: 7263–7275. 12072526

8. Sanchez AJ, Vincent MJ, Erickson BR, Nichol ST (2006) Crimean-congo hemorrhagic fever virus glycoprotein precursor is cleaved by Furin-like and SKI-1 proteases to generate a novel 38-kilodalton glycoprotein. J Virol 80: 514–525. doi: 10.1128/JVI.80.1.514-525.2006 16352575

9. Bergeron E, Albariño CG, Khristova ML, Nichol ST (2010) Crimean-Congo hemorrhagic fever virus-encoded ovarian tumor protease activity is dispensable for virus RNA polymerase function. J Virol 84: 216–226. doi: 10.1128/JVI.01859-09 19864393

10. Vincent M, Sanchez A, Erickson B, Basak A, Chretien M, et al. (2003) Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1. J Virol 77: 8640. 12885882

11. Bergeron E, Vincent MJ, Nichol ST (2007) Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity. J Virol 81: 13271–13276. doi: 10.1128/JVI.01647-07 17898072

12. Sanchez A, Yang ZY, Xu L, Nabel GJ, Crews T, et al. (1998) Biochemical analysis of the secreted and virion glycoproteins of Ebola virus. J Virol 72: 6442–6447. 9658086

13. Mallet WG, Maxfield FR (1999) Chimeric forms of furin and TGN38 are transported with the plasma membrane in the trans-Golgi network via distinct endosomal pathways. J Cell Biol 146: 345–359. 10465644

14. Albariño CG, Bergeron E, Erickson BR, Khristova ML, Rollin PE, et al. (2009) Efficient reverse genetics generation of infectious junin viruses differing in glycoprotein processing. J Virol 83: 5606–5614. doi: 10.1128/JVI.00276-09 19321606

15. Lowen AC, Noonan C, McLees A, Elliott RM (2004) Efficient bunyavirus rescue from cloned cDNA. Virology 330: 493–500. doi: 10.1016/j.virol.2004.10.009 15567443

16. Bergeron E, Chakrabarti AK, Bird BH, Dodd KA, McMullan LK, et al. (2012) Reverse genetics recovery of Lujo virus and role of virus RNA secondary structures in efficient virus growth. J Virol. doi: 10.1128/JVI.01144-12

17. Whelan SP, Ball LA, Barr JN, Wertz GT (1995) Efficient recovery of infectious vesicular stomatitis virus entirely from cDNA clones. Proc Natl Acad Sci USA 92: 8388–8392. 7667300

18. Raab D, Graf M, Notka F, Schödl T, Wagner R (2010) The GeneOptimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization. Syst Synth Biol 4: 215–225. doi: 10.1007/s11693-010-9062-3 21189842

19. Carter SD, Surtees R, Walter CT, Ariza A, Bergeron E, et al. (2012) Structure, Function, and Evolution of the Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein. J Virol 86: 10914–10923. doi: 10.1128/JVI.01555-12 22875964

20. Karlberg H, Tan Y-J, Mirazimi A (2011) Induction of caspase activation and cleavage of the viral nucleocapsid protein in different cell types during Crimean-Congo hemorrhagic fever virus infection. J Biol Chem 286: 3227–3234. doi: 10.1074/jbc.M110.149369 21123175

21. Habjan M, Penski N, Spiegel M, Weber F (2008) T7 RNA polymerase-dependent and-independent systems for cDNA-based rescue of Rift Valley fever virus. J Gen Virol 89: 2157–2166. doi: 10.1099/vir.0.2008/002097-0 18753225

22. Plyusnin A, Elliott RM (2011) Bunyaviridae. Horizon Scientific Press. 1 pp.

23. Volchkova VA, Klenk HD, Volchkov VE (1999) Delta-peptide is the carboxy-terminal cleavage fragment of the nonstructural small glycoprotein sGP of Ebola virus. Virology 265: 164–171. doi: 10.1006/viro.1999.0034 10603327

24. Volchkov VE, Feldmann H, Volchkova VA, Klenk HD (1998) Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc Natl Acad Sci USA 95: 5762–5767. 9576958

25. Neumann G, Geisbert TW, Ebihara H, Geisbert JB, Daddario-DiCaprio KM, et al. (2007) Proteolytic processing of the Ebola virus glycoprotein is not critical for Ebola virus replication in nonhuman primates. J Virol 81: 2995–2998. doi: 10.1128/JVI.02486-06 17229700

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: 406–410. 11739705

27. Gordon VM, Klimpel KR, Arora N, Henderson MA, Leppla SH (1995) Proteolytic activation of bacterial toxins by eukaryotic cells is performed by furin and by additional cellular proteases. Infect Immun 63: 82–87. 7806387

28. Seidah NG, Sadr MS, Chretien M, Mbikay M (2013) The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions. Journal of Biological Chemistry 288: 21473–21481. doi: 10.1074/jbc.R113.481549 23775089

29. Yang C, Skiena S, Futcher B, Mueller S, Wimmer E (2013) Deliberate reduction of hemagglutinin and neuraminidase expression of influenza virus leads to an ultraprotective live vaccine in mice. Proc Natl Acad Sci USA 110: 9481–9486. doi: 10.1073/pnas.1307473110 23690603

30. Mueller S, Coleman JR, Papamichail D, Ward CB, Nimnual A, et al. (2010) Live attenuated influenza virus vaccines by computer-aided rational design. Nat Biotechnol 28: 723–726. doi: 10.1038/nbt.1636 20543832

31. Gargili A, Thangamani S, Bente D (2013) Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and implications for an in vivo transmission model for Crimean-Congo hemorrhagic fever virus. Front Cell Infect Microbiol 3: 39. doi: 10.3389/fcimb.2013.00039 23971007

32. Bente D, Alimonti J, Shieh W, Camus G, Stroher U, et al. (2010) Pathogenesis and immune response of Crimean-Congo hemorrhagic fever virus in a STAT-1 knockout mouse model. J Virol 84: 11089. doi: 10.1128/JVI.01383-10 20739514

33. Albariño CG, Uebelhoer LS, Vincent JP, Khristova ML, Chakrabarti AK, et al. (2013) Development of a reverse genetics system to generate recombinant Marburg virus derived from a bat isolate. Virology 446: 230–237. doi: 10.1016/j.virol.2013.07.038 24074586

34. Bird BH, Albariño CG, Hartman AL, Erickson BR, Ksiazek TG, et al. (2008) Rift valley fever virus lacking the NSs and NSm genes is highly attenuated, confers protective immunity from virulent virus challenge, and allows for differential identification of infected and vaccinated animals. J Virol 82: 2681–2691. doi: 10.1128/JVI.02501-07 18199647