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 Vallée, I.
Right arrow Articles by Powell, P. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vallée, I.
Right arrow Articles by Powell, P. P.

 Previous Article  |  Next Article 

Journal of Virology, November 2001, p. 10372-10382, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10372-10382.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

African Swine Fever Virus Infection of Porcine Aortic Endothelial Cells Leads to Inhibition of Inflammatory Responses, Activation of the Thrombotic State, and Apoptosis

Isabelle Vallée,dagger Stephen W. G. Tait,Dagger and Penelope P. Powell*

Department of Immunology and Pathology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom

Received 7 May 2001/Accepted 29 July 2001

African swine fever (ASF) is an asymptomatic infection of warthogs and bushpigs, which has become an emergent disease of domestic pigs, characterized by hemorrhage, lymphopenia, and disseminated intravascular coagulation. It is caused by a large icosohedral double-stranded DNA virus, African swine fever virus (ASFV), with infection of macrophages well characterized in vitro and in vivo. This study shows that virulent isolates of ASFV also infect primary cultures of porcine aortic endothelial cells and bushpig endothelial cells (BPECs) in vitro. Kinetics of early and late gene expression, viral factory formation, replication, and secretion were similar in endothelial cells and macrophages. However, ASFV-infected endothelial cells died by apoptosis, detected morphologically by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and nuclear condensation and biochemically by poly(ADP-ribose) polymerase (PARP) cleavage at 4 h postinfection (hpi). Immediate-early proinflammatory responses were inhibited, characterized by a lack of E-selectin surface expression and interleukin 6 (IL-6) and IL-8 mRNA synthesis. Moreover, ASFV actively downregulated interferon-induced major histocompatibility complex class I surface expression, a strategy by which viruses evade the immune system. Significantly, Western blot analysis showed that the 65-kDa subunit of the transcription factor NF-kappa B, a central regulator of the early response to viral infection, decreased by 8 hpi and disappeared by 18 hpi. Both disappearance of NF-kappa B p65 and cleavage of PARP were reversed by the caspase inhibitor z-VAD-fmk. Interestingly, surface expression and mRNA transcription of tissue factor, an important initiator of the coagulation cascade, increased 4 h after ASFV infection. These data suggest a central role for vascular endothelial cells in the hemorrhagic pathogenesis of the disease. Since BPECs infected with ASFV also undergo apoptosis, resistance of the natural host must involve complex pathological factors other than viral tropism.

* Corresponding author. Mailing address: Department of Immunology and Pathology, Institute for Animal Health, Ash Road, Pirbright, Surrey GU24 ONF, United Kingdom. Phone: 1483 231090. Fax: 1483 232448. E-mail: penny.powell{at}bbsrc.ac.uk.

dagger Present address: UMR 956 BIPAR INRA-AFSSA-ENVA, AFSSA-Alfort, 94703 Maisons-Alfort, France.

Dagger Present address: Department of Cellular Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands.

Journal of Virology, November 2001, p. 10372-10382, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10372-10382.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Voehler, M. W., Eoff, R. L., McDonald, W. H., Guengerich, F. P., Stone, M. P. (2009). Modulation of the Structure, Catalytic Activity, and Fidelity of African Swine Fever Virus DNA Polymerase X by a Reversible Disulfide Switch. J. Biol. Chem. 284: 18434-18444 [Abstract] [Full Text]  
  • Shibamiya, A., Hersemeyer, K., Schmidt Woll, T., Sedding, D., Daniel, J.-M., Bauer, S., Koyama, T., Preissner, K. T., Kanse, S. M. (2009). A key role for Toll-like receptor-3 in disrupting the hemostasis balance on endothelial cells. Blood 113: 714-722 [Abstract] [Full Text]  
  • Bahl, K., Kim, S.-K., Calcagno, C., Ghersi, D., Puzone, R., Celada, F., Selin, L. K., Welsh, R. M. (2006). IFN-Induced Attrition of CD8 T Cells in the Presence or Absence of Cognate Antigen during the Early Stages of Viral Infections. J. Immunol. 176: 4284-4295 [Abstract] [Full Text]  
  • Stefanovic, S., Windsor, M., Nagata, K.-i., Inagaki, M., Wileman, T. (2005). Vimentin Rearrangement during African Swine Fever Virus Infection Involves Retrograde Transport along Microtubules and Phosphorylation of Vimentin by Calcium Calmodulin Kinase II. J. Virol. 79: 11766-11775 [Abstract] [Full Text]  
  • Netherton, C., Rouiller, I., Wileman, T. (2004). The Subcellular Distribution of Multigene Family 110 Proteins of African Swine Fever Virus Is Determined by Differences in C-Terminal KDEL Endoplasmic Reticulum Retention Motifs. J. Virol. 78: 3710-3721 [Abstract] [Full Text]  
  • Bensaude, E., Turner, J. L. E., Wakeley, P. R., Sweetman, D. A., Pardieu, C., Drew, T. W., Wileman, T., Powell, P. P. (2004). Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells. J. Gen. Virol. 85: 1029-1037 [Abstract] [Full Text]  
  • Afonso, C. L., Piccone, M. E., Zaffuto, K. M., Neilan, J., Kutish, G. F., Lu, Z., Balinsky, C. A., Gibb, T. R., Bean, T. J., Zsak, L., Rock, D. L. (2004). African Swine Fever Virus Multigene Family 360 and 530 Genes Affect Host Interferon Response. J. Virol. 78: 1858-1864 [Abstract] [Full Text]  
  • Geisbert, T. W., Young, H. A., Jahrling, P. B., Davis, K. J., Larsen, T., Kagan, E., Hensley, L. E. (2003). Pathogenesis of Ebola Hemorrhagic Fever in Primate Models: Evidence that Hemorrhage Is Not a Direct Effect of Virus-Induced Cytolysis of Endothelial Cells. Am. J. Pathol. 163: 2371-2382 [Abstract] [Full Text]  
  • Lin, Y., Bright, A. C., Rothermel, T. A., He, B. (2003). Induction of Apoptosis by Paramyxovirus Simian Virus 5 Lacking a Small Hydrophobic Gene. J. Virol. 77: 3371-3383 [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»