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 Feldmann, A.
Right arrow Articles by Klenk, H.-D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Feldmann, A.
Right arrow Articles by Klenk, H.-D.

 Previous Article  |  Next Article 

Journal of Virology, September 2000, p. 8018-8027, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Targeted Infection of Endothelial Cells by Avian Influenza Virus A/FPV/Rostock/34 (H7N1) in Chicken Embryos

Anke Feldmann,1 Martin K.-H. Schäfer,2 Wolfgang Garten,1 and Hans-Dieter Klenk1,*

Institut für Virologie1 and Institut für Anatomie und Zellbiologie,2 Philipps-Universität, Marburg, Germany

Received 15 February 2000/Accepted 26 May 2000

The tissue tropism and spread of infection of the highly pathogenic avian influenza virus A/FPV/Rostock/34 (H7N1) (FPV) were analyzed in 11-day-old chicken embryos. As shown by in situ hybridization, the virus caused generalized infection that was strictly confined to endothelial cells in all organs. Studies with reassortants of FPV and the apathogenic avian strain A/chick/Germany/N/49 (H10N7) revealed that endotheliotropism was linked to FPV hemagglutinin (HA). To further analyze the factors determining endotheliotropism, the HA-activating protease furin was cloned from chicken tissue. Ubiquitous expression of furin and other proprotein convertases in the chick embryo indicated that proteolytic activation of HA was not responsible for restriction of infection to the endothelium. To determine the expression of virus receptors in embryonic tissues, histochemical analysis of alpha 2,3- and alpha 2,6-linked neuraminic acid was carried out by lectin-binding assays. These receptors were found on endothelial cells and on several epithelial cells, but not on tissues surrounding endothelia. Finally, we analyzed the polarity of virus maturation in endothelial cells. Studies on cultured human endothelial cells employing confocal laser scanning microscopy revealed that HA is specifically targeted to the apical surface of these cells, and electron microscopy of embryonic tissues showed that virus maturation occurs also at the luminar side. Taken together, these observations indicate that endotheliotropism of FPV in the chicken embryo is determined, on one hand, by the high cleavability of HA, which mediates virus entry into the vascular system, and, on the other hand, by restricted receptor expression and polar budding, which prevent spread of infection into tissues surrounding endothelia.

* Corresponding author. Mailing address: Institut für Virologie, Postfach 2360, 35011 Marburg, Germany. Phone: 06421/28 66253. Fax: 06421/28 68962. E-mail: klenk{at}mailer.uni-marburg.de.

Journal of Virology, September 2000, p. 8018-8027, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Schmolke, M., Viemann, D., Roth, J., Ludwig, S. (2009). Essential Impact of NF-{kappa}B Signaling on the H5N1 Influenza A Virus-Induced Transcriptome. J. Immunol. 183: 5180-5189 [Abstract] [Full Text]  
  • Gabriel, G., Klingel, K., Planz, O., Bier, K., Herwig, A., Sauter, M., Klenk, H.-D. (2009). Spread of Infection and Lymphocyte Depletion in Mice Depends on Polymerase of Influenza Virus. Am. J. Pathol. 175: 1178-1186 [Abstract] [Full Text]  
  • Ito, K., Kim, K.-H., Lok, A. S.-F., Tong, S. (2009). Characterization of Genotype-Specific Carboxyl-Terminal Cleavage Sites of Hepatitis B Virus e Antigen Precursor and Identification of Furin as the Candidate Enzyme. J. Virol. 83: 3507-3517 [Abstract] [Full Text]  
  • Vascellari, M., Granato, A., Trevisan, L., Basilicata, L., Toffan, A., Milani, A., Mutinelli, F. (2007). Pathologic Findings of Highly Pathogenic Avian Influenza Virus A/Duck/Vietnam/12/05 (H5N1) in Experimentally Infected Pekin Ducks, Based on Immunohistochemistry and In Situ Hybridization. Vet Pathol 44: 635-642 [Abstract] [Full Text]  
  • Harvey, R., Martin, A. C. R., Zambon, M., Barclay, W. S. (2004). Restrictions to the Adaptation of Influenza A Virus H5 Hemagglutinin to the Human Host. J. Virol. 78: 502-507 [Abstract] [Full Text]  
  • Wichmann, D., Grone, H.-J., Frese, M., Pavlovic, J., Anheier, B., Haller, O., Klenk, H.-D., Feldmann, H. (2002). Hantaan Virus Infection Causes an Acute Neurological Disease That Is Fatal in Adult Laboratory Mice. J. Virol. 76: 8890-8899 [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»