This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andersson, I.
Right arrow Articles by Mirazimi, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andersson, I.
Right arrow Articles by Mirazimi, A.

 Previous Article  |  Next Article 

Journal of Virology, April 2004, p. 4323-4329, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4323-4329.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human MxA Protein Inhibits the Replication of Crimean-Congo Hemorrhagic Fever Virus

Ida Andersson,1 Linda Bladh,1 Mehrdad Mousavi-Jazi,1 Karl-Eric Magnusson,2 Åke Lundkvist,1,3 Otto Haller,4 and Ali Mirazimi1*

Center for Microbiological Preparedness/Swedish Institute for Infectious Disease Control, SE-171 82 Solna,1 Division of Medical Microbiology, Linköping University, SE-581 85 Linköping,2 MTC/Karolinska Institutet, SE-171 77 Stockholm, Sweden,3 Department of Virology, University of Freiburg, D-79008 Freiburg, Germany4

Received 19 August 2003/ Accepted 30 December 2003

Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Nairovirus within the family Bunyaviridae and is the causative agent of severe hemorrhagic fever. Despite increasing knowledge about hemorrhagic fever viruses, the factors determining their pathogenicity are still poorly understood. The interferon-induced MxA protein has been shown to have an inhibitory effect on several members of the Bunyaviridae family, but the effect of MxA against CCHFV has not previously been studied. Here, we report that human MxA has antiviral activity against CCHFV. The yield of progeny virus in cells constitutively expressing MxA was reduced up to 1,000-fold compared with control cells, and accumulation of viral genomes was blocked. Confocal microscopy revealed that MxA colocalizes with the nucleocapsid protein (NP) of CCHFV in the perinuclear regions of infected cells. Furthermore, we found that MxA interacted with NP by using a coimmunoprecipitation assay. We also found that an amino acid substitution (E645R) within the C-terminal domain of MxA resulted in a loss of MxA antiviral activity and, concomitantly, in the capacity to interact with CCHFV NP. These results suggest that MxA, by interacting with a component of the nucleocapsid, prevents replication of CCHFV viral RNA and thereby inhibits the production of new infectious virus particles.

* Corresponding author. Mailing address: Center for Microbiological Preparedness, Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden. Phone: 46 (8) 457 25 73. Fax: 46 (8) 30 79 57. E-mail: Ali.Mirazimi{at}smi.ki.se.

Journal of Virology, April 2004, p. 4323-4329, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4323-4329.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Netherton, C. L., Simpson, J., Haller, O., Wileman, T. E., Takamatsu, H.-H., Monaghan, P., Taylor, G. (2009). Inhibition of a Large Double-Stranded DNA Virus by MxA Protein. J. Virol. 83: 2310-2320 [Abstract] [Full Text]  
  • Peng, T., Zhu, J., Hwangbo, Y., Corey, L., Bumgarner, R. E. (2008). Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts. J. Virol. 82: 1934-1945 [Abstract] [Full Text]  
  • Porter, B. F., Ambrus, A., Storts, R. W. (2006). Immunohistochemical evaluation of mx protein expression in canine encephalitides.. Vet Pathol 43: 981-987 [Abstract] [Full Text]  
  • Boyd, A., Fazakerley, J. K., Bridgen, A. (2006). Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice. J. Gen. Virol. 87: 2005-2009 [Abstract] [Full Text]  
  • Kuno, G., Chang, G.-J. J. (2005). Biological Transmission of Arboviruses: Reexamination of and New Insights into Components, Mechanisms, and Unique Traits as Well as Their Evolutionary Trends. Clin. Microbiol. Rev. 18: 608-637 [Abstract] [Full Text]  
  • Akerstrom, S., Mousavi-Jazi, M., Klingstrom, J., Leijon, M., Lundkvist, A., Mirazimi, A. (2005). Nitric Oxide Inhibits the Replication Cycle of Severe Acute Respiratory Syndrome Coronavirus. J. Virol. 79: 1966-1969 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»