1887

Journal of General Virology header logo

Volume 103, Issue 7

Exogenous expression of both matrix protein and glycoprotein facilitates infectious viral particle production of Borna disease virus 1 No Access

Abstract

Borna disease virus 1 (BoDV-1) is a non-segmented, negative-strand RNA virus that is characterized by persistent infection in the nucleus and low production of progeny virions. This feature impedes not only the harvesting of infectious viral particles from infected cells but also the rescue of high titres of recombinant BoDV-1 (rBoDV-1) by reverse genetics. Here, we demonstrate that exogenous expression of both matrix protein (M) and glycoprotein (G), which are constituents of the viral lipid envelope, significantly facilitates the formation of infectious particles and propagation of BoDV-1 without affecting its viral RNA synthesis. Furthermore, simultaneous transfection of M and G expression plasmids with N, P and L helper plasmids by reverse genetics drastically enhances the rescue efficiency of rBoDV-1. On the other hand, we also show that overexpression of M induces obvious cytotoxicity similar to that of other Mononegaviruses. Together with our recent report showing that excess expression of G induces aberrant accumulation of immature G, a potential stimulator of the host innate immune response, it is conceivable that BoDV-1 may suppress excess expression of M and G to reduce the cytopathic effect, thereby leading to maintenance of persistent infection. Our results contribute not only to the establishment of an efficient method to recover high-titre BoDV-1 but also to understanding the unique mechanism of persistent BoDV-1 infection.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Borna disease virus , glycoprotein , matrix protein , reverse genetics and virus particle production
Funding
This study was supported by the:
  • Japan Society for the Promotion of Science (Award JP19K22530, JP20H05682, JP21K19909)
    • Principle Award Recipient: KeizoTomonaga
  • Japan Society for the Promotion of Science (Award JP19J23468)
    • Principle Award Recipient: TakehiroKanda
© 2022 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001767
2022-07-12
2024-04-25
Loading full text...

Full text loading...

References

  1. Kuhn JH, Adkins S, Alioto D, Alkhovsky SV, Amarasinghe GK et al. 2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Arch Virol 2020; 165:3023–3072 [View Article] [PubMed]
     [Google Scholar]
  2. Briese T, de la Torre JC, Lewis A, Ludwig H, Lipkin WI. Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. Proc Natl Acad Sci U S A 1992; 89:11486–11489 [View Article] [PubMed]
     [Google Scholar]
  3. Briese T, Schneemann A, Lewis AJ, Park YS, Kim S et al. Genomic organization of Borna disease virus. Proc Natl Acad Sci U S A 1994; 91:4362–4366 [View Article] [PubMed]
     [Google Scholar]
  4. Tomonaga K, Kobayashi T, Ikuta K. Molecular and cellular biology of Borna disease virus infection. Microbes Infect 2002; 4:491–500 [View Article] [PubMed]
     [Google Scholar]
  5. Chase G, Mayer D, Hildebrand A, Frank R, Hayashi Y et al. Borna disease virus matrix protein is an integral component of the viral ribonucleoprotein complex that does not interfere with polymerase activity. J Virol 2007; 81:743–749 [View Article] [PubMed]
     [Google Scholar]
  6. Cubitt B, de la Torre JC. Borna disease virus (BDV), a nonsegmented RNA virus, replicates in the nuclei of infected cells where infectious BDV ribonucleoproteins are present. J Virol 1994; 68:1371–1381 [View Article] [PubMed]
     [Google Scholar]
  7. Pauli G, Ludwig H. Increase of virus yields and releases of Borna disease virus from persistently infected cells. Virus Res 1985; 2:29–33 [View Article] [PubMed]
     [Google Scholar]
  8. Carbone KM, Rubin SA, Sierra-Honigmann AM, Lederman HM. Characterization of a glial cell line persistently infected with borna disease virus (BDV): influence of neurotrophic factors on BDV protein and RNA expression. J Virol 1993; 67:1453–1460 [View Article] [PubMed]
     [Google Scholar]
  9. Kanda T, Horie M, Komatsu Y, Tomonaga K. The Borna Disease Virus 2 (BoDV-2) Nucleoprotein Is a Conspecific Protein That Enhances BoDV-1 RNA-Dependent RNA Polymerase Activity. J Virol 2021; 95:e0093621 [View Article] [PubMed]
     [Google Scholar]
  10. Perez M, de la Torre JC. Identification of the Borna disease virus (BDV) proteins required for the formation of BDV-like particles. J Gen Virol 2005; 86:1891–1895 [View Article] [PubMed]
     [Google Scholar]
  11. Daito T, Fujino K, Honda T, Matsumoto Y, Watanabe Y et al. A novel borna disease virus vector system that stably expresses foreign proteins from an intercistronic noncoding region. J Virol 2011; 85:12170–12178 [View Article] [PubMed]
     [Google Scholar]
  12. Fujino K, Yamamoto Y, Daito T, Makino A, Honda T et al. Generation of a non-transmissive Borna disease virus vector lacking both matrix and glycoprotein genes. Microbiol Immunol 2017; 61:380–386 [View Article] [PubMed]
     [Google Scholar]
  13. Sakai M, Fujita Y, Komorizono R, Kanda T, Komatsu Y et al. Optimal expression of the envelope glycoprotein of orthobornaviruses determines the production of mature virus particles. J Virol 2020; 95:JVI.02221-20 [View Article] [PubMed]
     [Google Scholar]
  14. Gonzalez-Dunia D, Cubitt B, Grasser FA, de la Torre JC. Characterization of Borna disease virus p56 protein, a surface glycoprotein involved in virus entry. J Virol 1997; 71:3208–3218 [View Article] [PubMed]
     [Google Scholar]
  15. Gonzalez-Dunia D, Cubitt B, de la Torre JC. Mechanism of Borna disease virus entry into cells. J Virol 1998; 72:783–788 [View Article] [PubMed]
     [Google Scholar]
  16. Perez M, Watanabe M, Whitt MA, de la Torre JC. N-terminal domain of Borna disease virus G (p56) protein is sufficient for virus receptor recognition and cell entry. J Virol 2001; 75:7078–7085 [View Article] [PubMed]
     [Google Scholar]
  17. Schneider PA, Kim R, Lipkin WI. Evidence for translation of the Borna disease virus G protein by leaky ribosomal scanning and ribosomal reinitiation. J Virol 1997; 71:5614–5619 [View Article] [PubMed]
     [Google Scholar]
  18. Kojima S, Sato R, Yanai M, Komatsu Y, Horie M et al. Splicing-dependent subcellular targeting of Borna Disease virus nucleoprotein isoforms. J Virol 2019; 93:e01621-18 [View Article] [PubMed]
     [Google Scholar]
  19. Cubitt B, Oldstone C, Valcarcel J, Carlos de la Torre J. RNA splicing contributes to the generation of mature mRNAs of Borna disease virus, a non-segmented negative strand RNA virus. Virus Res 1994; 34:69–79 [View Article] [PubMed]
     [Google Scholar]
  20. Douzandegan Y, Tahamtan A, Gray Z, Nikoo HR, Tabarraei A et al. Cell death mechanisms in esophageal squamous cell carcinoma induced by vesicular stomatitis virus matrix protein. Osong Public Health Res Perspect 2019; 10:246–252 [View Article] [PubMed]
     [Google Scholar]
  21. Zan J, Liu J, Zhou J-W, Wang H-L, Mo K-K et al. Rabies virus matrix protein induces apoptosis by targeting mitochondria. Exp Cell Res 2016; 347:83–94 [View Article] [PubMed]
     [Google Scholar]
  22. Kojima I, Izumi F, Ozawa M, Fujimoto Y, Okajima M et al. Analyses of cell death mechanisms related to amino acid substitution at position 95 in the rabies virus matrix protein. J Gen Virol 2021; 102: [View Article] [PubMed]
     [Google Scholar]
  23. Décembre E, Assil S, Hillaire MLB, Dejnirattisai W, Mongkolsapaya J et al. Sensing of immature particles produced by dengue virus infected cells induces an antiviral response by plasmacytoid dendritic cells. PLoS Pathog 2014; 10:10 [View Article] [PubMed]
     [Google Scholar]
  24. Sinigaglia L, Gracias S, Décembre E, Fritz M, Bruni D et al. Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons. Sci Rep 2018; 8:10889 [View Article] [PubMed]
     [Google Scholar]
  25. Clinton GM, Little SP, Hagen FS, Huang AS. The matrix (M) protein of vesicular stomatitis virus regulates transcription. Cell 1978; 15:1455–1462 [View Article] [PubMed]
     [Google Scholar]
  26. Iwasaki M, Takeda M, Shirogane Y, Nakatsu Y, Nakamura T et al. The matrix protein of measles virus regulates viral RNA synthesis and assembly by interacting with the nucleocapsid protein. J Virol 2009; 83:10374–10383 [View Article] [PubMed]
     [Google Scholar]
  27. Ghildyal R, Baulch-Brown C, Mills J, Meanger J. The matrix protein of Human respiratory syncytial virus localises to the nucleus of infected cells and inhibits transcription. Arch Virol 2003; 148:1419–1429 [View Article] [PubMed]
     [Google Scholar]
  28. Hoenen T, Jung S, Herwig A, Groseth A, Becker S. Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription. Virology 2010; 403:56–66 [View Article] [PubMed]
     [Google Scholar]
  29. Watanabe K, Handa H, Mizumoto K, Nagata K. Mechanism for inhibition of influenza virus RNA polymerase activity by matrix protein. J Virol 1996; 70:241–247 [View Article] [PubMed]
     [Google Scholar]
  30. De BP, Thornton GB, Luk D, Banerjee AK. Purified matrix protein of vesicular stomatitis virus blocks viral transcription in vitro. Proc Natl Acad Sci U S A 1982; 79:7137–7141 [View Article] [PubMed]
     [Google Scholar]
  31. Wu L, Jin D, Wang D, Jing X, Gong P et al. The two-stage interaction of Ebola virus VP40 with nucleoprotein results in a switch from viral RNA synthesis to virion assembly/budding. Protein Cell 2022; 13:120–140 [View Article] [PubMed]
     [Google Scholar]
  32. Matsumoto Y, Hayashi Y, Omori H, Honda T, Daito T et al. Bornavirus closely associates and segregates with host chromosomes to ensure persistent intranuclear infection. Cell Host Microbe 2012; 11:492–503 [View Article] [PubMed]
     [Google Scholar]
  33. Cao S, Liu X, Yu M, Li J, Jia X et al. A nuclear export signal in the matrix protein of Influenza A virus is required for efficient virus replication. J Virol 2012; 86:4883–4891 [View Article] [PubMed]
     [Google Scholar]
  34. Martin K, Helenius A. Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell 1991; 67:117–130 [View Article] [PubMed]
     [Google Scholar]
  35. Akarsu H, Burmeister WP, Petosa C, Petit I, Müller CW et al. Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2). EMBO J 2003; 22:4646–4655 [View Article] [PubMed]
     [Google Scholar]
  36. Honda T, Tomonaga K. Nucleocytoplasmic shuttling of viral proteins in borna disease virus infection. Viruses 2013; 5:1978–1990 [View Article] [PubMed]
     [Google Scholar]
  37. Daito T, Fujino K, Watanabe Y, Ikuta K, Tomonaga K. Analysis of intracellular distribution of Borna disease virus glycoprotein fused with fluorescent markers in living cells. J Vet Med Sci 2011; 73:1243–1247 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001767
Loading
Exogenous expression of both matrix protein and glycoprotein facilitates infectious viral particle production of Borna disease virus 1
J. Gen. Virol. 103, 001767 (2022); https://doi.org/10.1099/jgv.0.001767
/content/journal/jgv/10.1099/jgv.0.001767
/content/journal/jgv/10.1099/jgv.0.001767
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error