1887

Abstract

The interferon-induced human MxA protein belongs to the dynamin superfamily of large GTPases and accumulates in the cytoplasm. MxA is a key component of the innate antiviral response and has previously been shown to inhibit several viruses with single-stranded RNA genomes of both polarities and a DNA virus. In addition, MxA also targets two double-stranded RNA viruses, and a mammalian reovirus as shown in this study. Thus, the antiviral spectrum of human MxA is broader than hitherto suspected. Interestingly, virus growth was not affected in cells expressing MxA(E645R), a mutant form of MxA that showed antiviral activity against orthomyxoviruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82526-0
2007-04-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/4/1319.html?itemId=/content/journal/jgv/10.1099/vir.0.82526-0&mimeType=html&fmt=ahah

References

  1. Balachandran S., Roberts P. C., Brown L. E., Truong H., Pattnaik A. K., Archer D. R., Barber G. N. 2000; Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity 13:129–141 [CrossRef]
    [Google Scholar]
  2. Bazzigher L., Schwarz A., Staeheli P. 1993; No enhanced influenza virus resistance of murine and avian cells expressing cloned duck Mx protein. Virology 195:100–112 [CrossRef]
    [Google Scholar]
  3. Birghan C., Mundt E., Gorbalenya A. E. 2000; A non-canonical Lon proteinase deficient of the ATPase domain employs the Ser-Lys catalytic dyad to impose broad control over the life cycle of a double-stranded RNA virus. EMBO J 19:114–123 [CrossRef]
    [Google Scholar]
  4. Chieux V., Chehadeh W., Harvey J., Haller O., Wattre P., Hober D. 2001; Inhibition of coxsackievirus B4 replication in stably transfected cells expressing human MxA protein. Virology 283:84–92 [CrossRef]
    [Google Scholar]
  5. De Benedetti A., Williams G. J., Comeau L., Baglioni C. 1985; Inhibition of viral mRNA translation in interferon-treated L cells infected with reovirus. J Virol 55:588–593
    [Google Scholar]
  6. Delmas B., Kibenge F. S. B., Leong J. C., Mundt E., Vakharia V. N., Wu J. L. 2004; Birnaviridae . In Virus Taxonomy, Eighth Report of the International Committee on Taxonomy of Viruses pp 561–569 Edited by Fauquet C. M., Mayo M. A., Maniloff J., Desselberger U., Ball L. A. London: Elsevier/Academic Press;
    [Google Scholar]
  7. Emeny J. M., Morgan M. J. 1979; Regulation of the interferon system: evidence that Vero cells have a genetic defect in interferon production. J Gen Virol 43:247–252 [CrossRef]
    [Google Scholar]
  8. Flohr F., Schneider-Schaulies S., Haller O., Kochs G. 1999; The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures. FEBS Lett 463:24–28 [CrossRef]
    [Google Scholar]
  9. Frese M., Kochs G., Meier-Dieter U., Sielber J., Haller O. 1995; Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus. J Virol 69:3904–3909
    [Google Scholar]
  10. Frese M., Kochs G., Feldmann H., Hertkorn C., Haller O. 1996; Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein. J Virol 70:915–923
    [Google Scholar]
  11. Gordien E., Rosmorduc O., Peltekian C., Garreau F., Brechot C., Kremsdorf D. 2001; Inhibition of hepatitis B virus replication by the interferon-inducible MxA protein. J Virol 75:2684–2691 [CrossRef]
    [Google Scholar]
  12. Granzow H., Birghan Ch., Mettenleiter T. C., Beyer J., Köllner B., Mundt E. 1997; A second form of infectious bursal disease virus-associated tubules contains VP4. J Virol 71:8879–8885
    [Google Scholar]
  13. Horisberger M. A. 1992; Interferon-induced human protein MxA is a GTPase which binds transiently to cellular proteins. J Virol 66:4705–4709
    [Google Scholar]
  14. Kaerber G. 1931; Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Arch Exp Pathol Pharmakol 162:480–483(in German;
    [Google Scholar]
  15. Ko J. H., Jin H. K., Asano A., Takada A., Ninomiya A., Kida H., Hokiyama H., Ohara M., Tsuzuki M. other authors 2002; Polymorphisms and the differential antiviral activity of the chicken Mx gene. Genome Res 12:595–601 [CrossRef]
    [Google Scholar]
  16. Ko J. H., Takada A., Mitsuhashi T., Agui T., Watanabe T. 2004; Native antiviral specificity of chicken Mx protein depends on amino acid variation at position 631. Anim Genet 35:119–122 [CrossRef]
    [Google Scholar]
  17. Kochs G., Haller O. 1999a; GTP-bound human MxA protein interacts with the nucleocapsids of Thogoto virus (Orthomyxoviridae). J Biol Chem 274:4370–4376 [CrossRef]
    [Google Scholar]
  18. Kochs G., Haller O. 1999b; Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids. Proc Natl Acad Sci U S A 96:2082–2086 [CrossRef]
    [Google Scholar]
  19. Kochs G., Janzen C., Hohenberg H., Haller O. 2002; Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. Proc Natl Acad Sci U S A 99:3153–3158 [CrossRef]
    [Google Scholar]
  20. Landis H., Simon-Jodicke A., Kloti A., Di Paolo C., Schnorr J. J., Schneider-Schaulies S., Hefti H. P., Pavlovic J. 1998; Human MxA protein confers resistance to Semliki Forest virus and inhibits the amplification of a Semliki Forest virus-based replicon in the absence of viral structural proteins. J Virol 72:1516–1522
    [Google Scholar]
  21. Larsen R., Rokenes T. P., Robertsen B. 2004; Inhibition of infectious pancreatic necrosis virus replication by Atlantic salmon Mx1 protein. J Virol 78:7938–7944 [CrossRef]
    [Google Scholar]
  22. Lee S.-H., Vidal S. M. 2002; Functional diversity of Mx proteins: variations on a theme of host resistance to infection. Genome Res 12:527–530 [CrossRef]
    [Google Scholar]
  23. Li X. L., Blackford J. A., Hassel B. A. 1998; RNase L mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. J Virol 72:2752–2759
    [Google Scholar]
  24. Mundt E. 1999; Tissue culture infectivity of different strains of infectious bursal disease virus is determined by distinct amino acids in VP2. J Gen Virol 80:2067–2076
    [Google Scholar]
  25. Mundt E., Kollner B., Kretzschmar D. 1997; VP5 of infectious bursal disease virus is not essential for viral replication in cell culture. J Virol 71:5647–5651
    [Google Scholar]
  26. Mundt E., de Haas N., van Loon A. A. 2003; Development of a vaccine for immunization against classical as well as variant strains of infectious bursal disease virus using reverse genetics. Vaccine 21:4616–4624 [CrossRef]
    [Google Scholar]
  27. Pavlovic J., Züricher T., Haller O., Staeheli P. 1990; Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. J Virol 64:3370–3375
    [Google Scholar]
  28. Ponten A., Sick C., Weeber M., Haller O., Kochs G. 1997; Dominant-negative mutants of human MxA protein: domains in the carboxy-terminal moiety are important for oligomerization and antiviral activity. J Virol 71:2591–2599
    [Google Scholar]
  29. Reichelt M., Stertz S., Krijnse-Locker J., Haller O., Kochs G. 2004; Missorting of La Crosse virus nucleocapsid protein by the interferon-induced MxA GTPase involves smooth ER membranes. Traffic 5:772–784 [CrossRef]
    [Google Scholar]
  30. Schneider-Schaulies S., Schneider-Schaulies J., Schuster A., Bayer M., Pavlovic J., ter Meulen V. 1994; Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells. J Virol 68:6910–6917
    [Google Scholar]
  31. Schnorr J. J., Schneider-Schaulies S., Simon-Jodicke A., Pavlovic J., Horisberger M. A., ter Meulen V. 1993; MxA-dependent inhibition of measles virus glycoprotein synthesis in a stably transfected human monocytic cell line. J Virol 67:4760–4768
    [Google Scholar]
  32. Schwemmle M., Weining K. C., Richter M. F., Schumacher B., Staehli P. 1995; Vesicular stomatitis virus transcription inhibited by purified MxA protein. Virology 206:545–554 [CrossRef]
    [Google Scholar]
  33. Smith J. A., Schmechel S. C., Williams B. R. G., Silverman R. H., Schiff L. A. 2005; Involvement of the interferon-regulated antiviral proteins PKR and RNase L in reovirus-induced shutoff of cellular translation. J Virol 79:2240–2250 [CrossRef]
    [Google Scholar]
  34. Tyler K. L. 2001; Mammalian reoviruses. In Fields Virology , 4th edn. pp 1729–1945 Edited by Knipe D. M., Howley P. M. Philadelphia, USA: Lippincott Williams & Wilkins;
    [Google Scholar]
  35. Tytell A. A., Lampson G. P., Field A. K., Hilleman M. R. 1967; Inducers of interferon and host resistence. III. Double-stranded RNA from Reovirus type 3 virions (reo-3-RNA). Proc Natl Acad Sci U S A 58:1719–1722 [CrossRef]
    [Google Scholar]
  36. Weber F., Haller O., Kochs G. 2000; MxA GTPase blocks reporter gene expression of reconstituted Thogoto virus ribonucleoprotein complexes. J Virol 74:560–563 [CrossRef]
    [Google Scholar]
  37. Zürcher T., Pavlovic J., Staehli P. 1992; Mechanism of human MxA protein action: variants with changed antiviral properties. EMBO J 11:1657–1661
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82526-0
Loading
/content/journal/jgv/10.1099/vir.0.82526-0
Loading

Data & Media loading...

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