Apoptosis in natural rabies virus infection in dogs

Open access

Abstract

Introduction: In the present study apoptosis was investigated in the cornu ammonis and cerebellum of 10 dogs naturally infected with rabies virus. Diagnosis of rabies was based on the results of fluorescent antibody staining and experimental inoculation.

Material and Methods: The paraffin tissue sections were stained with haematoxylin and eosin, avidin-biotin complex peroxidase (ABC-P), and terminal deoxynucleotidyl transferase biotin-dUTP nick end-labelling (TUNEL) methods.

Results: Histopathological examination revealed encephalomyelitis of varying severity and the presence of Negri bodies. Dense rabies antigens were determined in the motor neurons with ABC-P method. On the other hand, Bcl-2 protein and Bax protein gave positive reaction in seven and five cases, respectively. TUNEL staining demonstrated very marked apoptotic changes in the nuclei of neurons localised deep in the substantia alba of the cerebellum. Similar changes were also determined in perivascular mononuclear cells and glia cells within the substantia alba. No apoptopic changes were found in the motor neurons of the cornu ammonis.

Conclusion: The absence of apoptotic changes in the neurons was considered to be the consequence of the necrotic changes that developed in these neurons.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Arnoult D. Skaletskaya A. Estaquier J. Dufour C. Goldmacher V.S.: The murine cytomegalovirus cell death suppressor m38.5 binds Bax and blocks Bax-mediated mitochondrial outer membrane permeabilization. Apoptosis 2008 13 1100–1110.

  • 2. Aubert M. Pomeranz L.E. Blaho J.A.: Herpes simplex virus blocks apoptosis by precluding mitochondrial cytochrome c release independent of caspase activation in infected human epithelial cells. Apoptosis 2007 12 19–35.

  • 3. Benjamin M.D. Glenn F.R. Mathiass J.S.: Everything you always wanted to know about rabies virus (But were afraid to ask). Annu Rev Virol 2015 2 451–471.

  • 4. Baloul L. Lafon M.: Apoptosis and rabies virus neuroinvasion. Biochimie 2003 85 777–788.

  • 5. Bredesen D.E.: Neural apoptosis. Ann Neur 1995 38 839–851.

  • 6. Cooper B.J.: Disease at the cellular level. In: Mechanism of disease a textbook of comparative general pathology edited by D.O. Slauson B.J. Cooper Mosby USA 2002 pp. 16–76.

  • 7. Elmore S.: Apoptosis: A review of programmed cell death. Toxicol Pathol 2007 35 495–516.

  • 8. Gomes-Leal W. Marthins L.C. Diniz J.A. Dos Santos Z.A. Borges J.A. Macedo C.A. Medeiros A.C. De Paula L.S. Guimarães J.S. Freire M.A. Vasconcelos P.F. Picanço-Diniz C.W.: Neurotropism and neuropathological effects of selected rhabdoviruses on intranasally-infected newborn mice. Acta Tropica 2006 97 126–139.

  • 9. Jackson A.C.: Apoptosis in experimental rabies in bax-deficient mice. Acta Neuropathol 1999 98 288–294.

  • 10. Jackson A.C. Park H.: Apoptotic cell death in experimental rabies in suckling mice. Acta Neuropathol 1998 95 159–164.

  • 11. Jackson A.C. Randle E. Lawrance G. Rossiter J.P.: Neuronal apoptosis does not play an important role in human rabies encephalitis. J Neurovirol 2008 14 368–375.

  • 12. Jackson A.C. Rossiter J.P.: Apoptosis plays in important role in experimental rabies virus infection. J Virol 1997 71 5603–5607.

  • 13. Jafari A.I. Sankian M. Ahmadpour S. Varasteh A.R. Haghir H.: Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats. Exp Diabetes Res 2008 12 Article ID 638467.

  • 14. Kennedy P.G.E.: Viruses apoptosis and neuroinflammation a double-edged sword. J Neurovirol 2015 21 1–7.

  • 15. Knobel D.L. Cleaveland S. Coleman P.G. Fevre E.M. Meltzer M.I. Miranda M.E. Shaw A. Zinsstag J. Meslin F.X.: Re-evaluating the burden of rabies in Africa and Asia. Bull World Health Org 2005 83 360–368.

  • 16. Lewis J. Wesselingh S.L. Griffin D.E. Hardwick J.M.: Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence. J Virol 1996 70 1828–1835.

  • 17. Mathers C.D. Ezzati M. Lopez A.D.: Measuring the burden of neglected tropical diseases: The global burden of disease framework. Plos neglected Trop Dis 2007 1 1–15.

  • 18. Maxie M.G. Youssef S.: Lyssavirus infections. In: Jubb Kennedy and Palmer’s Pathology of Domestic Animals/Nervous system edited by G.M. Maxie Saunders Elsevier Edinburgh 2007 pp. 413–416.

  • 19. Norbury C.J. Hickson I.D.: Cellular responses to DNA damage. Annu Rev Pharmacol Toxicol 2001 41 367–401.

  • 20. Pollack M. Leeuwenburgh C.: Mitochondrial control of apoptosis in aging and exercise. http://grove.ufl.edu/~cleeuwen/mtapoptosis.html. 2009.

  • 21. Suja M.S. Mahadevan A. Madhusudana S.N. Shankar S.K.: Role of apoptosis in rabies viral encephalitis: a comparative study in mice canine and human brain with a review of literature. Path Res Intern 2011 Article ID 374286.

  • 22. Sun X.M. MacFarlane M. Zhuang J. Wolf B.B. Green D.R. Cohen G.M.: Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem 1999 274: 5053–5060.

  • 23. Thompson C.B.: Apoptosis in the pathogenesis and treatment of disease. Science 1995 267 1456–1462.

  • 24. Townsend S.E. Lembo T. Cleaveland S. Meslin F.X. Miranda M.E. Putra A.A. Haydon D.T. Hampson K.: Surveillance guidelines for disease elimination: A case study of canine rabies. Comp Immunol Microbiol Infect Dis 2013 36 249–261.

  • 25. Vural Atalay S.: The comparison of histopathological immunoperoxidase and immunofluorescence techniques in the diagnosis of rabies in dogs. Eurasian J Vet Sci 1999 15 35–50.

  • 26. Vural Atalay S. Alcigir G. Berkin S.: Immunohistochemical and histopathological studies of fixed rabies virus in goats. Onderstepoort J Vet Res 2001 68 83–89.

  • 27. Yan X. Prosniak M. Curtis M.T. Weiss M.L. Faber M. Dietzschold B. Fu Z.F.: Silver-haired bat rabies virus variant does not induce apoptosis in the brain of experimentally infected mice. J Neurovirol 2001 7 518–527.

Search
Journal information
Impact Factor

IMPACT FACTOR J Vet Res 2018: 0.829
5-year IMPACT FACTOR: 0.938

CiteScore 2018: 0.68

SCImago Journal Rank (SJR) 2018: 0.291
Source Normalized Impact per Paper (SNIP) 2018: 0.501

Metrics
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 342 178 11
PDF Downloads 164 91 6