Download PDF
Thromb Haemost 2003; 90(02): 326-334
DOI: 10.1160/TH02-09-0043
Wound Healing and Inflammation/Infection
Schattauer GmbH

Endothelial cell function alteration after Junin virus infection

Ricardo Martin Gomez   *
2   Department of Microbiology, Faculty of Medicine, University of Buenos Aires, CONICET, Argentina
,
Roberto Gabriel Pozner   *
1   Department of Thrombosis and Hemostasis, Hematological Research Institute, National Academy of Medicine, National Research Council (CONICET), Buenos Aires, Argentina
,
Maria Angela Lazzari
1   Department of Thrombosis and Hemostasis, Hematological Research Institute, National Academy of Medicine, National Research Council (CONICET), Buenos Aires, Argentina
,
Lina Paola D’Atri
1   Department of Thrombosis and Hemostasis, Hematological Research Institute, National Academy of Medicine, National Research Council (CONICET), Buenos Aires, Argentina
,
Soledad Negrotto
1   Department of Thrombosis and Hemostasis, Hematological Research Institute, National Academy of Medicine, National Research Council (CONICET), Buenos Aires, Argentina
,
Ana Marisa Chudzinski-Tavassi
3   Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, Brazil
,
María Isabel Berría
2   Department of Microbiology, Faculty of Medicine, University of Buenos Aires, CONICET, Argentina
,
Mirta Schattner
1   Department of Thrombosis and Hemostasis, Hematological Research Institute, National Academy of Medicine, National Research Council (CONICET), Buenos Aires, Argentina
› Author AffiliationsFinancial support: This work was supported by grants from the René Baron Foundation, CONICET, SECyT, ministry of Health and Antorchas Foundation. *Ricardo Martin Gomez and Roberto Gabriel Pozner contributed equally to this work.
Further Information

Publication History

Received 09 September 2002

Accepted after revision 12 May 2003

Publication Date:
06 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Hematologic involvement is the main feature of Argentine hemorrhagic fever (AHF), an endemo-epidemic disease caused by Junin virus (JV). Since endothelial dysfunction could play a role in AHF-altered hemostasis, we studied human umbilical vein endothelial cell (HUVEC) infection with a virulent (JVv) and a non-virulent (JVa) JV strain. Cells were infected by the two JV variants with no detectable apoptosis or cytopathic effect. Both viral variants up-regulated ICAM-1 and VCAM-1 levels, while von Willebrand factor (VWF) production was decreased. Prostacyclin (PGI2) release and decay accelerating factor (DAF) expression were greater in JVv- than in JVa-infected or control cells. Furthermore, nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) expression was only raised in JVv-infected supernatants. Significant NO and PGI2 values were also detected in AHF patient sera.

These data demonstrate that endothelial cell responses are triggered subsequently by JV infection, suggesting that such alterations play a major role in the pathogenesis of AHF and perhaps in other viral-induced hemorrhagic diseases.

Keywords

Cell adhesion molecules - von Willebrand factor - prostacyclin - nitric oxide

* Ricardo Martin Gomez and Roberto Gabriel Pozner contributed equally to this work.


 

  • References

  • 1 Mills JN, Ellis BA, Childs JE. et al. Prevalence of infection with Junin virus in rodent populations in the epidemic area of Argentine hemorrhagic fever. Am J Trop Med Hyg 1994; 51: 554-62.
    CrossrefPubMedSearch in Google Scholar
  • 2 Vainrub B, Salas R. Latin American hemorrhagic fever. Infect Dis Clin North Am 1994; 8: 47-59.
    CrossrefPubMedSearch in Google Scholar
  • 3 Maiztegui JI, Fernandez NJ, de Damilano AJ. Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome. Lancet 1979; 2: 1216-7.
    CrossrefPubMedSearch in Google Scholar
  • 4 Enria DA, Briggiler AM, Fernandez NJ. et al. Importance of dose of neutralising antibodies in treatment of Argentine haemorrhagic fever with immune plasma. Lancet 1984; 2: 255-6.
    CrossrefPubMedSearch in Google Scholar
  • 5 Enria DA, Maiztegui JI. Antiviral treatment of Argentine hemorrhagic fever. Antiviral Res 1994; 23: 23-31.
    CrossrefPubMedSearch in Google Scholar
  • 6 Maiztegui JI, McKee Jr. KT , Barrera Oro JG. et al. Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group. J Infect Dis 1998; 177: 277-83.
    CrossrefPubMedSearch in Google Scholar
  • 7 Harrison LH, Halsey NA, McKee Jr. KT . et al. Clinical case definitions for Argentine hemorrhagic fever. Clin Infect Dis 1999; 28: 1091-4.
    CrossrefPubMedSearch in Google Scholar
  • 8 de Bracco MM, Rimoldi MT, Cossio PM. et al. Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response. N Engl J Med 1978; 299: 216-21.
    CrossrefPubMedSearch in Google Scholar
  • 9 Heller MV, Marta RF, Sturk A. et al. Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever. Thromb Haemost 1995; 73: 368-73.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Cummins D, Molinas FC, Lerer G. et al. A plasma inhibitor of platelet aggregation in patients with Argentine hemorrhagic fever. Am J Trop Med Hyg 1990; 42: 470-5.
    CrossrefPubMedSearch in Google Scholar
  • 11 Cummins D, Fisher-Hoch SP, Walshe KJ. et al. A plasma inhibitor of platelet aggregation in patients with Lassa fever. Br J Haematol 1989; 72: 543-8.
    CrossrefPubMedSearch in Google Scholar
  • 12 Lukashevich IS, Maryankova R, Vladyko AS. et al. Lassa and Mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on IL-8 and TNF-alpha gene expression. J Med Virol 1999; 59: 552-60.
    CrossrefPubMedSearch in Google Scholar
  • 13 Hippenstiel S, Suttorp N. Interaction of pathogens with the endothelium. Thromb Haemost 2003; 89: 18-24.
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Peters CJ, Zaki SR. Role of the endothelium in viral hemorrhagic fevers. Crit Care Med 2002; 30: S268-S273.
    CrossrefPubMedSearch in Google Scholar
  • 15 Andrews BS, Theofilopoulos AN, Peters CJ. et al. Replication of Dengue and Junin viruses in cultured rabbit and human endothelial cells. Infect Immun 1978; 20: 776-81.
    CrossrefPubMedSearch in Google Scholar
  • 16 Albarino CG, Ghiringhelli PD, Posik DM. et al. Molecular characterization of attenuated Junin virus strains. J Gen Virol 1997; 78: 1605-10.
    CrossrefPubMedSearch in Google Scholar
  • 17 Kenyon RH, Green DE, Maiztegui JI. et al. Viral strain dependent differences in experimental Argentine hemorrhagic fever (Junin virus) infection of guinea pigs. Intervirology 1988; 29: 133-43.
    CrossrefPubMedSearch in Google Scholar
  • 18 Jaffe EA, Nachman RL, Becker CG. et al. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-56.
    CrossrefPubMedSearch in Google Scholar
  • 19 Gomez RM, Yep A, Schattner M. et al. Junin virus-induced astrocytosis is impaired by iNOS inhibition. J Med Virol 2003; 69: 145-9.
    CrossrefPubMedSearch in Google Scholar
  • 20 Sanchez A, Pifat DY, Kenyon RH. et al. Junin virus monoclonal antibodies: characterization and cross-reactivity with other arenaviruses. J Gen Virol 1989; 70: 1125-32.
    CrossrefPubMedSearch in Google Scholar
  • 21 Wang AM, Creasey AA, Ladner MB. et al. Molecular cloning of the complementary DNA for human tumor necrosis factor. Science 1985; 228: 149-54.
    CrossrefPubMedSearch in Google Scholar
  • 22 Schattner M, Pozner RG, Engelberger I. et al. Effect of nitric oxide on megakaryocyte growth induced by thrombopoietin. J Lab Clin Med 2001; 137: 261-9.
    CrossrefPubMedSearch in Google Scholar
  • 23 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424.
    CrossrefPubMedSearch in Google Scholar
  • 24 Tan L, Kowalska MA, Romo GM. et al. Identification and characterization of endothelial glycoprotein Ib using viper venom proteins modulating cell adhesion. Blood 1999; 93: 2605-16.
    CrossrefPubMedSearch in Google Scholar
  • 25 Wu G, Essex DW, Meloni FJ. et al. Human endothelial cells in culture and in vivo express on their surface all four components of the glycoprotein Ib/IX/V complex. Blood 1997; 90: 2660-9.
    CrossrefPubMedSearch in Google Scholar
  • 26 Heller MV, Saavedra MC, Falcoff R. et al. Increased tumor necrosis factor-alpha levels in Argentine hemorrhagic fever. J Infect Dis 1992; 166: 1203-4.
    CrossrefPubMedSearch in Google Scholar
  • 27 Marker O, Scheynius A, Christensen JP. et al. Virus-activated T cells regulate expression of adhesion molecules on endothelial cells in sites of infection. J Neuroimmunol 1995; 62: 35-42.
    CrossrefPubMedSearch in Google Scholar
  • 28 Anderson R, Wang S, Osiowy C. et al. Activation of endothelial cells via antibody-enhanced Dengue virus infection of peripheral blood monocytes. J Virol 1997; 71: 4226-32.
    CrossrefPubMedSearch in Google Scholar
  • 29 Krishnaswamy G, Kelley J, Yerra L. et al. Human endothelium as a source of multifunctional cytokines: molecular regulation and possible role in human disease. J Interferon Cytokine Res 1999; 19: 91-104.
    CrossrefPubMedSearch in Google Scholar
  • 30 Molinas FC, Maiztegui JI. Factor VIII: C and factor VIII R: Ag in Argentine hemorrhagic fever. Thromb Haemost 1981; 46: 525-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Kroll J, Waltenberger J. VEGF-A induces expression of eNOS and iNOS in endothelial cells via VEGF receptor-2 (KDR). Biochem Biophys Res Commun 1998; 252: 743-6.
    CrossrefPubMedSearch in Google Scholar
  • 32 Orpana A, Ranta V, Mikkola T. et al. Inducible nitric oxide and prostacyclin productions are differently controlled by extracellular matrix and cell density in human vascular endothelial cells. J Cell Biochem 1997; 64: 538-46.
    CrossrefPubMedSearch in Google Scholar
  • 33 Rosenkranz-Weiss P, Sessa WC, Milstien S. et al. Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in terahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest 1994; 93: 2236-43.
    CrossrefPubMedSearch in Google Scholar
  • 34 Spiller OB, Morgan BP, Tufaro F. et al. Altered expression of host-encoded complement regulators on human cytomegalo-virus-infected cells. Eur J Immunol 1996; 26: 1532-8.
    CrossrefPubMedSearch in Google Scholar
  • 35 Spear GT, Lurain NS, Parker CJ. et al. Host cell-derived complement control proteins CD55 and CD59 are incorporated into the virions of two unrelated enveloped viruses. Human T cell leukemia/lymphoma virus type I (HTLV-I) and human cytomegalovirus (HCMV). J Immunol 1995; 155: 4376-81.
    CrossrefPubMedSearch in Google Scholar