1887

Abstract

Although the Enders strain of mumps virus (MuV) encodes a functional V protein that acts as an interferon (IFN) antagonist, in multi-cycle growth assays MuV Enders grew poorly in naïve (‘IFN-competent’ Hep2) cells but grew to high titres in ‘IFN-compromised’ Hep2 cells. Even so, the growth rate of MuV Enders was significantly slower in ‘IFN-compromised’ Hep2 cells when compared with its replication rate in Vero cells and with the replication rate of parainfluenza virus type 5 (a closely related paramyxovirus) in both naïve and ‘IFN-compromised’ Hep2 cells. This suggests that a consequence of slower growth is that the IFN system of naïve Hep2 cells can respond quickly enough to control the growth of MuV Enders. This is supported by the finding that rapidly growing variants of MuV Enders that were selected on ‘IFN-compromised’ Hep2 cells (i.e. in the absence of any selection pressure exerted by the IFN response) also grew to high titres on naïve Hep2 cells. Sequencing of the complete genome of one of these variants identified a single point mutation that resulted in a substitution of a conserved asparagine by histidine at position 498 of the haemagglutinin–neuraminidase protein, although this mutation was not present in all rapidly growing variants. These results support the concept that there is a race between the ability of a cell to detect and respond to virus infection and the ability of a virus to block the IFN response. Importantly, this emphasizes that factors other than viral IFN antagonists influence the sensitivity of viruses to IFN.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.013722-0
2009-11-01
2019-11-12
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/11/2731.html?itemId=/content/journal/jgv/10.1099/vir.0.013722-0&mimeType=html&fmt=ahah

References

  1. Andrejeva, J., Childs, K. S., Young, D. F., Carlos, T. S., Stock, N., Goodbourn, S. & Randall, R. E. ( 2004; ). The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-β promoter. Proc Natl Acad Sci U S A 101, 17264–17269.[CrossRef]
    [Google Scholar]
  2. Brown, D. D., Rima, B. K., Allen, I. V., Baron, M. D., Banyard, A. C., Barrett, T. & Duprex, W. P. ( 2005; ). Rational attenuation of a morbillivirus by modulating the activity of the RNA-dependent RNA polymerase. J Virol 79, 14330–14338.[CrossRef]
    [Google Scholar]
  3. Carlos, T. S., Fearns, R. & Randall, R. E. ( 2005; ). Interferon-induced alterations in the pattern of parainfluenza virus 5 transcription and protein synthesis and the induction of virus inclusion bodies. J Virol 79, 14112–14121.[CrossRef]
    [Google Scholar]
  4. Carlos, T. S., Young, D., Stertz, S., Kochs, G. & Randall, R. E. ( 2007; ). Interferon-induced inhibition of parainfluenza virus type 5; the roles of MxA, PKR and oligo A synthetase/RNase L. Virology 363, 166–173.[CrossRef]
    [Google Scholar]
  5. Chatziandreou, N., Stock, N., Young, D., Andrejeva, J., Hagmaier, K., McGeoch, D. J. & Randall, R. E. ( 2004; ). Relationships and host range of human, canine, simian and porcine isolates of simian virus 5 (parainfluenza virus 5). J Gen Virol 85, 3007–3016.[CrossRef]
    [Google Scholar]
  6. Childs, K., Stock, N., Ross, C., Andrejeva, J., Hilton, L., Skinner, M., Randall, R. & Goodbourn, S. ( 2007; ). mda-5, but not RIG-I, is a common target for paramyxovirus V proteins. Virology 359, 190–200.[CrossRef]
    [Google Scholar]
  7. Choppin, P. W. ( 1964; ). Multiplication of a myxovirus (Sv5) with minimal cytopathic effects and without interference. Virology 23, 224–233.[CrossRef]
    [Google Scholar]
  8. Demaison, C., Parsley, K., Brouns, G., Scherr, M., Battmer, K., Kinnon, C., Grez, M. & Thrasher, A. J. ( 2002; ). High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter. Hum Gene Ther 13, 803–813.[CrossRef]
    [Google Scholar]
  9. Desmyter, J., Melnick, J. L. & Rawls, W. E. ( 1968; ). Defectiveness of interferon production and of rubella virus interference in a line of African green monkey kidney cells (Vero). J Virol 2, 955–961.
    [Google Scholar]
  10. Didcock, L., Young, D. F., Goodbourn, S. & Randall, R. E. ( 1999; ). The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J Virol 73, 9928–9933.
    [Google Scholar]
  11. Dillon, P. J. & Parks, G. D. ( 2007; ). Role for the phosphoprotein p subunit of the paramyxovirus polymerase in limiting induction of host cell antiviral responses. J Virol 81, 11116–11127.[CrossRef]
    [Google Scholar]
  12. Enders, J. F., Levens, J. H., Stokes, J., Jr, Maris, E. P. & Berenberg, W. ( 1946; ). Attenuation of virulence with retention of antigenicity of mumps virus after passage in the embryonated egg. J Immunol 54, 283–291.
    [Google Scholar]
  13. Grimm, D., Staeheli, P., Hufbauer, M., Koerner, I., Martínez-Sobrido, L., Solórzano, A., García-Sastre, A., Haller, O. & Kochs, G. ( 2007; ). Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc Natl Acad Sci U S A 104, 6806–6811.[CrossRef]
    [Google Scholar]
  14. Haller, O., Kochs, G. & Weber, F. ( 2006; ). The interferon response circuit: induction and suppression by pathogenic viruses. Virology 344, 119–130.[CrossRef]
    [Google Scholar]
  15. Hanke, T., Szawlowski, P. & Randall, R. E. ( 1992; ). Construction of solid matrix–antibody–antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen. J Gen Virol 73, 653–660.[CrossRef]
    [Google Scholar]
  16. Hilton, L., Moganeradj, K., Zhang, G., Chen, Y. H., Randall, R. E., McCauley, J. W. & Goodbourn, S. ( 2006; ). The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation. J Virol 80, 11723–11732.[CrossRef]
    [Google Scholar]
  17. Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K. K. & other authors ( 2006; ). 5′-Triphosphate RNA is the ligand for RIG-I. Science 314, 994–997.[CrossRef]
    [Google Scholar]
  18. Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T. S., Fujita, T. & Akira, S. ( 2008; ). Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205, 1601–1610.[CrossRef]
    [Google Scholar]
  19. Kubota, T., Yokosawa, N., Yokota, S. & Fujii, N. ( 2001; ). C terminal CYS-RICH region of mumps virus structural V protein correlates with block of interferon α and γ signal transduction pathway through decrease of STAT 1-α. Biochem Biophys Res Commun 283, 255–259.[CrossRef]
    [Google Scholar]
  20. Lamb, R. A. & Parks, G. D. ( 2006; ). Paramyxoviridae: the Viruses and their Replication, 5th edn. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams and Wilkins.
  21. McCarthy, M., Jubelt, B., Fay, D. B. & Johnson, R. T. ( 1980; ). Comparative studies of five strains of mumps virus in vitro and in neonatal hamsters: evaluation of growth, cytopathogenicity, and neurovirulence. J Med Virol 5, 1–15.[CrossRef]
    [Google Scholar]
  22. Mosca, J. D. & Pitha, P. M. ( 1986; ). Transcriptional and posttranscriptional regulation of exogenous human beta interferon gene in simian cells defective in interferon synthesis. Mol Cell Biol 6, 2279–2283.
    [Google Scholar]
  23. Nakatsu, Y., Takeda, M., Ohno, S., Shirogane, Y., Iwasaki, M. & Yanagi, Y. ( 2008; ). Measles virus circumvents the host interferon response by different actions of the C and V proteins. J Virol 82, 8296–8306.[CrossRef]
    [Google Scholar]
  24. Nishio, M., Garcin, D., Simonet, V. & Kolakofsky, D. ( 2002; ). The carboxyl segment of the mumps virus V protein associates with STAT proteins in vitro via a tryptophan-rich motif. Virology 300, 92–99.[CrossRef]
    [Google Scholar]
  25. Pichlmair, A., Schulz, O., Tan, C. P., Naslund, T. I., Liljestrom, P., Weber, F. & Reis e Sousa, C. ( 2006; ). RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314, 997–1001.[CrossRef]
    [Google Scholar]
  26. Platanias, L. C. ( 2005; ). Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5, 375–386.[CrossRef]
    [Google Scholar]
  27. Plotkin, S. A. ( 2004; ). Mumps vaccine. In Vaccines, 4th edn, pp. 441–470. Edited by S. A. Plotkin & W. A. Orenstein. Philadelphia: W. B. Saunders.
  28. Plumet, S., Duprex, W. P. & Gerlier, D. ( 2005; ). Dynamics of viral RNA synthesis during measles virus infection. J Virol 79, 6900–6908.[CrossRef]
    [Google Scholar]
  29. Puri, M., Lemon, K., Duprex, W. P., Rima, B. K. & Horvath, C. M. ( 2009; ). A point mutation, E95D, in the mumps virus V protein disengages STAT3 targeting from STAT1 targeting. J Virol 83, 6347–6356.[CrossRef]
    [Google Scholar]
  30. Randall, R. E. & Dinwoodie, N. ( 1986; ). Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol 67, 2163–2177.[CrossRef]
    [Google Scholar]
  31. Randall, R. E. & Goodbourn, S. ( 2008; ). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89, 1–47.[CrossRef]
    [Google Scholar]
  32. Sanz-Ramos, M., Díaz-San Segundo, F., Escarmís, C., Domingo, E. & Sevilla, N. ( 2008; ). Hidden virulence determinants in a viral quasispecies in vivo. J Virol 82, 10465–10476.[CrossRef]
    [Google Scholar]
  33. Silin, D., Lyubomska, O., Ludlow, M., Duprex, W. P. & Rima, B. K. ( 2007; ). Development of a challenge-protective vaccine concept by modification of the viral RNA-dependent RNA polymerase of canine distemper virus. J Virol 81, 13649–13658.[CrossRef]
    [Google Scholar]
  34. Takeuchi, O. & Akira, S. ( 2009; ). Innate immunity to virus infection. Immunol Rev 227, 75–86.[CrossRef]
    [Google Scholar]
  35. Timani, K. A., Sun, D., Sun, M., Keim, C., Lin, Y., Schmitt, P. T., Schmitt, A. P. & He, B. ( 2008; ). A single amino acid residue change in the P protein of parainfluenza virus 5 (PIV5) elevates viral gene expression. J Virol 82, 9123–9133.[CrossRef]
    [Google Scholar]
  36. Ulane, C. M., Rodriguez, J. J., Parisien, J. P. & Horvath, C. M. ( 2003; ). STAT3 ubiquitylation and degradation by mumps virus suppress cytokine and oncogene signaling. J Virol 77, 6385–6393.[CrossRef]
    [Google Scholar]
  37. Yokosawa, N., Yokota, S., Kubota, T. & Fujii, N. ( 2002; ). C-terminal region of STAT-1α is not necessary for its ubiquitination and degradation caused by mumps virus V protein. J Virol 76, 12683–12690.[CrossRef]
    [Google Scholar]
  38. Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S. & Fujita, T. ( 2004; ). The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5, 730–737.[CrossRef]
    [Google Scholar]
  39. Young, D. F., Andrejeva, L., Livingstone, A., Goodbourn, S., Lamb, R. A., Collins, P. L., Elliott, R. M. & Randall, R. E. ( 2003; ). Virus replication in engineered human cells that do not respond to interferons. J Virol 77, 2174–2181.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.013722-0
Loading
/content/journal/jgv/10.1099/vir.0.013722-0
Loading

Data & Media loading...

Most Cited This Month

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