Thromb Haemost 1995; 73(01): 112-117
DOI: 10.1055/s-0038-1653734
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

The Role of Fibrinolysis in the Pathogenesis of the Haemorrhagic Syndrome Produced by Virulent Isolates of African Swine Fever Virus

C J Villeda
1   The Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
,
J C Gómez-Villamandos
2   Departamento de Anatomía y Anatomía Patológica Comparada, Facultad de Veterinaria, Universidad de Córdoba, Córdoba, Spain
,
S M Williams
3   The Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey, UK
,
J Hervás
2   Departamento de Anatomía y Anatomía Patológica Comparada, Facultad de Veterinaria, Universidad de Córdoba, Córdoba, Spain
,
P J Wilkinson
3   The Institute for Animal Health, Pirbright Laboratory, Pirbright, Surrey, UK
,
E Viñuela
1   The Centro de Biología Molecular (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
› Author Affiliations
Further Information

Publication History

Received 10 May 1994

Accepted after revision 27 September 1994

Publication Date:
09 July 2018 (online)

Summary

The activity of several proteins involved in fibrinolysis and the morphological changes in the blood vessel walls of pigs infected with highly virulent (Malawi’83) and moderately virulent (Dominican Republic ‘78-DR’78) ASF virus isolates were determined. Pigs infected with the Malawi’83 virus developed an increased fibrinolytic activity due to high plasma levels of tissue-plasminogen activator (t-PA) of 71.3 ± 22.8 IU/ml (mean ± SD), which correlated well with an increased activation of interstitial capillary endothelial cells and high levels of 1150 ± 73.6 nM of fibrin monomer in the circulation. Animals infected with DR’78 virus, in contrast, showed an inhibition of fibrinolysis in the late stages of disease with almost a 5-fold increase of plasminogen activator inhibitor (PAI) activity of 196.0 AU/ml. These results suggest that activation of the fibrinolytic system in pigs infected with the Malawi’83 virus is probably due to increased formation and deposition of fibrin in the circulation, contributing to an increased bleeding tendency and higher mortality. On the contrary, animals infected with DR’78 virus developed an inhibition of fibrinolysis and thus a reduction in bleeding.

 
  • References

  • 1 Viñuela E. Molecular biology of African swine fever virus. In: African swine fever. Becker Y. ed. Martinus Nijhoff; Boston, USA: 1997. pp 31-49
  • 2 Hess WR. African swine fever: a reassessment. Adv Vet Sci Comp Med 1981; 25: 39-69
  • 3 Breese SS, DeBoer CJ. Electron microscopy observations of African swine fever virus in tissue culture cells. Virology 1996; 28: 420-428
  • 4 Carrascosa JL, Carazo JM, Carrascosa AL, Garcia N, Santisteban A, Viñuela E. General morphology and capsid fine structure of African swine fever virus particles. Virology 1994; 132: 160-172
  • 5 Villeda CJ, Williams SM, Wilkinson PJ, Viñuela E. Haemostatic abnormalities in African swine fever. A comparison of two virus strains of different virulence (Dominican Republic ’78 and Malta ’78) Arch Virol 1993; 130: 71-83
  • 6 Villeda CJ, Williams SM, Wilkinson PJ, Viñuela E. Consumption coagulopathy associated with shock in acute African swine fever. Arch Virol 1993; 133: 467-475
  • 7 Cosgriff TM, Morrill JC, Jennings GB, Hodgson LA, Slayter MV, Gibbs PH, Peters CJ. Hemostatic derangement produced by Rift valley fever virus in rhesus monkeys. Rev Infect Dis 1999; 11 (04) 807-814
  • 8 Lee M, Kim B-K, Kim S, Park S, Han JS, Kim ST, Lee JS. Coagulopathy in hemorrhagic fever with renal syndrome (Korean hemorrhagic fever). Rev Infect Dis 1999; 11 (04) 877-883
  • 9 Halstead SB. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: A pathogenetic cascade. Rev Infect Dis 1999; 11 (04) 830-839
  • 10 Cosgriff TM. Viruses and hemostasis. Rev Infect Dis 1999; 11 (04) 672-688
  • 11 Sierra MA, Quezada M, Fernandez A, Carrasco L, Gomez-Villamandos JC, Martin de las Mulas J, Sanchez-Vizcaino JM. Experimental African swine fever: evidence of the virus in interstitial tissues of kidney. Vet Pathol 1999; 26: 173-176
  • 12 Sierra MA, Bemabe A, Mozos E, Mendez A, Jover A. Ultrastructure of the liver in pigs with experimental African swine fever. Vet Pathol 1997; 24: 460-462
  • 13 Enjuanes L, Cubero I, Viñuela E. Sensitivity of macrophages from different species to African swine fever (ASF) virus. J Gen Virol 1997; 34: 455-463
  • 14 Mebus CA, McVicar JW, Dardiri AH. Comparison of the pathology of high and low virulence African swine fever virus infections. In: African Swine Fever. Wilkinson PJ. ed. EUR 8466 EN, Proc. CEC/FAO Research Seminar; Sardinia: 09/1991. pp 183-194
  • 15 Bachmann F, Kruithof EK O. Tissue plasminogen activator: chemical and physiological aspects. Semin Thromb Hemost 1994; 10: 6-17
  • 16 Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci USA 1993; 80: 2956-2960
  • 17 Krauthausen E, Drommer W, Sierra MA, Jover A. Light and electron microscopical findings on the intestine in spontaneous and experimentally induced African swine fever (ASF). Dtsch Tierärztl Wschr 1992; 99: 54-59
  • 18 Fernandez A, Perez J, Martin de las Mulas J, Carrasco L, Dominguez J, Sierra MA. Localization of African swine fever viral antigen, swine IgM, IgG and C1 q in lung and liver tissues of experimentally infected pigs. J Comp Pathol 1992; 107: 81-90
  • 19 Haresnape JM. African swine fever in Malawi. Trop Animal Health Prod 1994; 16: 123-125
  • 20 Wilkinson PJ, Donaldson AI, Greig A, Bruce W. Transmission studies with African swine fever virus. Infection of pigs by airborne virus J Comp Pathol 1997; 87: 487-495
  • 21 Malmquist WA, Hay D. Hemadsorption and cytopathic effect produced by African swine fever virus in swine bone marrow and buffy coat cultures. Am J Vet Res 1990; 21: 104-109
  • 22 Nilsson K, Rosén S, Friberger P. A new kit for the determination of tissue plasminogen activator and its inhibitor in blood. Fibrinolysis 1997; 1: 163-168
  • 23 Welles EG, Prasse KW, Duncan A. Chromogenic assay for equine plasminogen. Am J Vet Res 1990; 51: 1080-1085
  • 24 Wiman B, Rånby M. Determination of soluble fibrin in plasma by a rapid and quantitative spectrophotometric assay. Thromb Haemost 1996; 55: 189-193
  • 25 Rossi GL. Simple apparatus for perfusion fixation for electron microscopy. Experientia 1995; 31: 998
  • 26 Funahara Y, Shirahata A. Sumarmo. Coagulopathy in DHF/DSS and elimination of the risk factor. ICMR Annual 1995; 5: 9-15
  • 27 Kaplan KL, Bini A, Fenogloi Jr J, Kudryk B. Fibrin and the vessel wall. In: Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis. Liu CY, Cien S. eds. Plenum Press; 1990. New York, London; pp 313-318
  • 28 Chmielewska J, Rånby M, Wiman B. Kinetic of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Biochem J 1998; 25: 327-332
  • 29 Li XZ, Jin XM, Li H. Semi-thin sections and electron microscopy in epidemic hemorrhagic fever. Transactions of Ha Er Bin Medical University 1994; 3: 43-46
  • 30 Booth NA, Anderson JA, Bennett B. Platelet release protein which inhibits plasminogen activators. J Clin Pathol 1995; 38: 825-830
  • 31 Sprengers ED, Princen HM G, Kooistra T, van Hinsbergh VW. Inhibition of plasminogen activators by conditioned medium of human hepatocytes and hepatoma cell line Hep G2. J Lab Clin Med 1995; 105: 751-758
  • 32 Edwards JF, Dodds WJ, Slauson DO. Coagulation changes in African swine fever virus infection. Am J Vet Res 1994; 45: 2414-2420
  • 33 Krishnamurti C, Larry MW, Alving BM. Stimulation of plasminogen activator inhibitor activity in human monocytes infected with Dengue virus. Am J Trop Med 1999; 40 (01) 102-107