1887

Abstract

We investigated the spread of glycoprotein gE (gE)- negative pseudorabies virus (PRV) and its rescued ‘wild- type’ strain into and within the central nervous system (CNS) of 3- and 10-week-old pigs. This is the first study that demonstrates PRV invasion of the porcine CNS via the synaptically linked neurons of the olfactory and trigeminal routes and that demonstrates the role of gE in this invasion. After intranasal inoculation with high doses of virus, gE-negative PRV replicated less efficiently in peripheral tissues. The titres of the gE-negative virus in the oropharyngeal mucosa, olfactory epithelium, draining lymph nodes and trigeminal ganglion were approximately 100-fold lower in 3-week-old pigs and 10fold lower in 10-week-old pigs than titres of the ‘wild- type’ virus. In contrast to the ‘wild-type’ virus, titres of the gE-negative virus were very low or undetectable in the olfactory bulb, brain stem and other tissues of the CNS. Viral antigen of rescued ‘wild-type’ PRV and of gE-negative PRV was detected immunohistochemically in the olfactory epithelium and in neurons of the trigeminal ganglion, and also in the olfactory and trigeminal axons leading towards the CNS. But, in contrast to ‘wild-type’ virus, no viral antigen of the gEnegative virus was detected in second- or third-order neurons in the olfactory bulb or in the brain stem. We conclude that gE-negative PRV can infect first-order neurons of the olfactory and trigeminal routes and is able to spread via their axons towards the CNS. Yet, gEnegative PRV has a greatly reduced capacity to infect second- or third-order neurons. Finally, we report lateral spread of ‘wild-type ’ PRV in the trigeminal ganglion, i.e. nonsynaptic transport from neuron to neuron. Possible mechanisms that could explain the reduced levels of the gE-negative virus in the CNS are discussed.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-11-3095
1994-11-01
2022-05-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/11/JV0750113095.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-11-3095&mimeType=html&fmt=ahah

References

  1. Baskerville A., Mcferran J. B., Dow C. 1973; Aujeszky’s disease in pigs. Veterinary Bulletin 43:465–480
    [Google Scholar]
  2. Card J. P., Rinaman L., Schwaber J. S., Miselis R. R., Whealy M. E., Robbins A. K., Enquist L. W. 1990; Neurotropic properties of pseudorabies virus: uptake and transneuronal passage in the rat central nervous system. Journal of Neuroscience 10:1974–1994
    [Google Scholar]
  3. Card J. P., Whealy M. E., Robbins A. K., Enquist L. W. 1992; Pseudorabies virus envelope glycoprotein gl influences both neurotropism and virulence during infection of the rat visual system. Journal of Neuroscience 66:3032–3041
    [Google Scholar]
  4. Card J. P., Rinaman L., Lynn R. B., Lee B. -H., Meade R. P., Miselis R. R., Enquist L. W. 1993; Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport, and pathogenesis. Journal of Neuroscience 13:2515–2539
    [Google Scholar]
  5. Dow C., Mcferran J. B. 1962; The neuropathology of Aujeszky’s disease in the pig. Research in Veterinary Science 3:436–442
    [Google Scholar]
  6. Devries S. H., Baylor D. A. 1993; Synaptic circuitry of the retina and olfactory bulb. Cell 72/ Neuron 10 Suppl 139–149
    [Google Scholar]
  7. Dingwell K. S., Brunetti G. R., Hendricks R. L., Tang O., Tang M., Rainbow A. J., Johnson D. C. 1994; Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. Journal of Virology 68:834–845
    [Google Scholar]
  8. Gustafson D. P. 1986; Pseudorabies. In Diseases of Swine pp 274–289 Leman A. D., Straw B., Glock R. D., Mengeling W. L., Penny R. H. C., Scholl E. Edited by Ames: Iowa State University Press;
    [Google Scholar]
  9. Heffner S., Kovacs F., Klupp B. G., Mettenleiter T. C. 1993; Glycoprotein gp50-negative pseudorabies virus: a novel approach towards a nonspreading live herpes vaccine. Journal of Virology 67:1529–1537
    [Google Scholar]
  10. Jacobs L., Rziha H. J., Kimman T. G., Gielkens A. L. J., Vanoirschot J. T. 1993a; Deleting valine-125 and cysteine-126 in glycoprotein gl of pseudorabies virus strain NIA-3 decreases plaque size and reduces virulence in mice. Archives of Virology 131:251–264
    [Google Scholar]
  11. Jacobs L., Mulder W. A. M., Vanoirschot J. T., Gielkens A. L. J., Kimman T. G. 1993b; Deleting two amino acids in glycoprotein gl of pseudorabies virus decreases virulence and neurotropism for pigs, but does not affect immunogenicity. Journal of General Virology 74:2201–2206
    [Google Scholar]
  12. Kasza L., Shadduck J. A., Christofinis G. J. 1971; Establishment, viral susceptibility, and biological characteristics of a swine kidney cell line SK-6. Research in Veterinary Science 13:46–51
    [Google Scholar]
  13. Kimman T. G., Dewind N., Oei-Lie N., Pol J. M. A., Berns A. J. M., Gielkens A. L. J. 1992; Contribution of single genes within the unique short region of Aujeszky’s disease virus (suid herpesvirus type 1) to virulence, pathogenesis and immunogenicity. Journal of General Virology 73:243–251
    [Google Scholar]
  14. Kuypers H. G. J. M., Ugolini G. 1990; Viruses as transneuronal tracers. Trends in Neurosciences 13:71–75
    [Google Scholar]
  15. Lomniczi B., Wantanabe S., Ben-Porat T., Kaplan A. S. 1987; Genome location and identification of functions defective in the Bartha vaccine strain of pseudorabies virus. Journal of Virology 61:796–801
    [Google Scholar]
  16. Mccracken R. M., Mcferran J. B., Dow C. 1973; The neural spread of pseudorabies virus in calves. Journal of General Virology 20:17–28
    [Google Scholar]
  17. Mcferran J. B., Dow C. 1975; Studies on immunization of pigs with the Bartha strain of Aujeszky’s disease virus. Research in Veterinary Science 19:17–22
    [Google Scholar]
  18. Martin J. B., Dolivo M. 1983; Neuronal and transneuronal tracing in the trigeminal system of the rat using herpes virus suis. Brain Research 273:253–276
    [Google Scholar]
  19. Mettenleiter T. C. 1991; Molecular biology of pseudorabies (Aujeszky’s disease) virus. Comparative Immunology and Infectious Diseases 14:151–163
    [Google Scholar]
  20. Mettenleiter T. C., Zsak L., Kaplan A. S., Ben-Porat T., Lomniczi B. 1987a; Role of a structural glycoprotein of pseudorabies virus in virus virulence. Journal of Virology 61:4030–4032
    [Google Scholar]
  21. Mettenleiter T. C., Schreurs C., Zuckermann F., Ben-Porat T. 1987b; Role of pseudorabiesvirus glycoprotein gl in release from infected cells. Journal of Virology 61:2764–2769
    [Google Scholar]
  22. Peeters B., De Wind N., Broer R., Gielkens A., Moormann R. 1992; Glycoprotein H of pseudorabies virus is essential for entry and cell-to-cell spread of the virus. Journal of Virology 66:3888–3892
    [Google Scholar]
  23. Peeters B., Pol J., Gielkens A., Moormann R. 1993; Envelope glycoprotein gp50 of pseudorabies virus is essential for virus entry but is not required for viral spread in mice. Journal of Virology 67:170–177
    [Google Scholar]
  24. Pensaert M. B., Kluge J. P. 1989; Pseudorabies virus (Aujeszky’s disease). In Virus Infections of Porcines pp 39–64 Pensaert M. B. Edited by Amsterdam: Elsevier Science Publishers;
    [Google Scholar]
  25. Pol J. M. A., Gielkens A. L. J., Van Oirschot J. T. 1989; Comparative pathogenesis of three stains of pseudorabies virus in pigs. Microbial Pathogenesis 7:361–371
    [Google Scholar]
  26. Pol J. M. A., Quint W. G. V., Kok G. L., Broekhuysen-Davies J. M. 1991; Pseudorabies virus infection in explants of porcine nasal mucosa. Research in Veterinary Science 50:45–53
    [Google Scholar]
  27. Rziha H. J., Mettenleiter T. C., Ohlinger V., Wittmann G. 1986; Herpesvirus (pseudorabies virus) latency in swine: occurrence and physical state of the DNA in neural tissues. Virology 155:600–613
    [Google Scholar]
  28. Strack A. M., Loewy A. D. 1990; Pseudorabies virus: a highly specific transneuronal cell body marker in the sympathetic nervous system. Journal of Neuroscience 10:2139–2147
    [Google Scholar]
  29. Venable J. H., Coggeshall R. 1965; A simplified lead citrate stain for use in electron microscopy. Journal of Cell Biology 25:407–408
    [Google Scholar]
  30. Wagenaar F., Kok G. L., Broekhuisen-Davies J. M., Pol J. M. A. 1993; Rapid cold fixation of tissue samples by microwave irradiation for use in electron microscopy. Histochemical Journal 25:719–725
    [Google Scholar]
  31. Whealy M. E., Card J. P., Robbins A. K., Dubbin J. R., Rziha H. J., Enquist L. W. 1993; Specific pseudorabies virus infection of the rat visual system requires both gl and gp63 glycoproteins. Journal of Virology 67:3786–3797
    [Google Scholar]
  32. Zsak L., Mettenleiter T. C., Stugg N., Ben-Porat T. 1989; Release of pseudorabies from infected cells is controlled by several viral functions and is modulated by cellular components. Journal of Virology 63:5475–5477
    [Google Scholar]
  33. Zsak L., Zuckermann F., Stugg N., Ben-Porat T. 1992; Glycoprotein gl of pseudorabies virus promotes cell fusion and virus spread via direct cell-to-cell transmission. Journal of General Virology 66:2316–2325
    [Google Scholar]
  34. Zuckermann F. A., Mettenleiter T. C., Scheurs C., Sugg N., Ben-Porat T. 1988; Complex between glycoproteins gl and gp63 of pseudorabies virus: its effect on virus replication. Journal of Virology 62:4622–4626
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-11-3095
Loading
/content/journal/jgv/10.1099/0022-1317-75-11-3095
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error