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. 1984 Oct;52(1):198–205. doi: 10.1128/jvi.52.1.198-205.1984

Genetic basis of the neurovirulence of pseudorabies virus.

B Lomniczi, S Watanabe, T Ben-Porat, A S Kaplan
PMCID: PMC254506  PMID: 6090697

Abstract

Lomniczi et al. (J. Virol. 49:970-979, 1984) have shown previously that two attenuated vaccine strains of pseudorabies virus have a similar deletion in the short unique (US) region of the genome. The region which is deleted normally codes for several translationally competent mRNAs. As expected, these mRNAs are not formed in the cells infected with the vaccine strains. The function specified by these mRNAs is thus not necessary for growth in cell culture. Using intracerebral inoculation of 1-day-old chicks as a test system, we have attempted to determine whether a gene within the region that is missing from the attenuated strains specifies functions that are required for the expression of virulence. An analysis of recombinants between the Bartha vaccine strain and a virulent pseudorabies virus strain (having or lacking a thymidine kinase gene [TK+ or TK-]) revealed the following. None of the recombinant plaque isolates that were either TK- or which had a deletion in the US was virulent. Not all recombinant plaque isolates which were both TK+ and had an intact US were virulent. These results indicate that both thymidine kinase activity and an intact US were necessary but not sufficient for the expression of virulence. Marker rescue experiments involving cotransfection of the Bartha strain DNA and a restriction fragment spanning the region of the genome that was missing from the Bartha strain resulted in the isolation of virions to which an intact US had been restored. These virions were not virulent but had an improved ability to replicate in the brains of chicks compared with that of the parental nonrescued Bartha strain. Our results show that genes in the US region, which are missing from the Bartha strain, were necessary for virulence but that this strain was also defective in other genes required for the expression of virulence. Thus, the virulence of pseudorabies virus, as measured by intracerebral inoculation into chicks, appears to be controlled multigenically.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben-Porat T., Demarchi J. M., Kaplan A. S. Characterization of defective interfering viral particles present in a population of pseudorabies virions. Virology. 1974 Sep;61(1):29–37. doi: 10.1016/0042-6822(74)90239-6. [DOI] [PubMed] [Google Scholar]
  2. Ben-Porat T., Veach R. A., Ihara S. Localization of the regions of homology between the genomes of herpes simplex virus, type 1, and pseudorabies virus. Virology. 1983 May;127(1):194–204. doi: 10.1016/0042-6822(83)90383-5. [DOI] [PubMed] [Google Scholar]
  3. Centifanto-Fitzgerald Y. M., Yamaguchi T., Kaufman H. E., Tognon M., Roizman B. Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA. J Exp Med. 1982 Feb 1;155(2):475–489. doi: 10.1084/jem.155.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Deatly A. M., Feldman L. T., Ben-Porat T. The large late virus transcripts synthesized in herpesvirus suis (pseudorabies) virus-infected cells are not precursors of mRNA. Virology. 1984 Jun;135(2):452–465. doi: 10.1016/0042-6822(84)90200-9. [DOI] [PubMed] [Google Scholar]
  5. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  6. Field H. J., Wildy P. The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (Lond) 1978 Oct;81(2):267–277. doi: 10.1017/s0022172400025109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Isle H. B., Venkatesan S., Moss B. Cell-free translation of early and late mRNAs selected by hybridization to cloned DNA fragments derived from the left 14 million to 72 million daltons of the vaccinia virus genome. Virology. 1981 Jul 15;112(1):306–317. doi: 10.1016/0042-6822(81)90636-x. [DOI] [PubMed] [Google Scholar]
  8. KAPLAN A. S. A study of the herpes simplex virus-rabbit kidney cell system by the plaque technique. Virology. 1957 Dec;4(3):435–457. doi: 10.1016/0042-6822(57)90078-8. [DOI] [PubMed] [Google Scholar]
  9. KAPLAN A. S., VATTER A. E. A comparison of herpes simplex and pseudorabies viruses. Virology. 1959 Apr;7(4):394–407. doi: 10.1016/0042-6822(59)90068-6. [DOI] [PubMed] [Google Scholar]
  10. Ladin B. F., Ihara S., Hampl H., Ben-Porat T. Pathway of assembly of herpesvirus capsids: an analysis using DNA+ temperature-sensitive mutants of pseudorabies virus. Virology. 1982 Jan 30;116(2):544–561. doi: 10.1016/0042-6822(82)90147-7. [DOI] [PubMed] [Google Scholar]
  11. Lomniczi B. Biological properties of Aujeszky's disease (pseudorabies) virus strains with special regard to interferon production and interferon sensitivity. Arch Gesamte Virusforsch. 1974;44(3):205–214. doi: 10.1007/BF01240608. [DOI] [PubMed] [Google Scholar]
  12. Lomniczi B., Blankenship M. L., Ben-Porat T. Deletions in the genomes of pseudorabies virus vaccine strains and existence of four isomers of the genomes. J Virol. 1984 Mar;49(3):970–979. doi: 10.1128/jvi.49.3.970-979.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Paul P. S., Mengeling W. L., Pirtle E. C. Differentiation of pseudorabies (Aujeszky's disease) virus strains by restriction endonuclease analysis. Arch Virol. 1982;73(2):193–198. doi: 10.1007/BF01314727. [DOI] [PubMed] [Google Scholar]
  14. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  15. Platt K. B., Maré C. J., Hinz P. N. Differentiation of vaccine strains and field isolates of pseudorabies (Aujeszky's disease) virus: thermal sensitivity and rabbit virulence markers. Arch Virol. 1979;60(1):13–23. doi: 10.1007/BF01318093. [DOI] [PubMed] [Google Scholar]
  16. Price R. W., Khan A. Resistance of peripheral autonomic neurons to in vivo productive infection by herpes simplex virus mutants deficient in thymidine kinase activity. Infect Immun. 1981 Nov;34(2):571–580. doi: 10.1128/iai.34.2.571-580.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  18. Rixon F. J., Ben-Porat T. Structural evolution of the DNA of pseudorabies-defective viral particles. Virology. 1979 Aug;97(1):151–163. doi: 10.1016/0042-6822(79)90381-7. [DOI] [PubMed] [Google Scholar]
  19. Rott R. Molecular basis of infectivity and pathogenicity of myxovirus. Brief review. Arch Virol. 1979;59(4):285–298. doi: 10.1007/BF01317469. [DOI] [PubMed] [Google Scholar]
  20. Rozhon E. J., Gensemer P., Shope R. E., Bishop D. H. Attenuation of virulence of a bunyavirus involving an L RNA defect and isolation of LAC/SSH/LAC and LAC/SSH/SSH reassortants. Virology. 1981 May;111(1):125–138. doi: 10.1016/0042-6822(81)90659-0. [DOI] [PubMed] [Google Scholar]
  21. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  22. Tenser R. B., Dunstan M. E. Herpes simplex virus thymidine kinase expression in infection of the trigeminal ganglion. Virology. 1979 Dec;99(2):417–422. doi: 10.1016/0042-6822(79)90021-7. [DOI] [PubMed] [Google Scholar]
  23. Tenser R. B., Ressel S. J., Fralish F. A., Jones J. C. The role of pseudorabies virus thymidine kinase expression in trigeminal ganglion infection. J Gen Virol. 1983 Jun;64(Pt 6):1369–1373. doi: 10.1099/0022-1317-64-6-1369. [DOI] [PubMed] [Google Scholar]
  24. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thompson R. L., Stevens J. G. Biological characterization of a herpes simplex virus intertypic recombinant which is completely and specifically non-neurovirulent. Virology. 1983 Nov;131(1):171–179. doi: 10.1016/0042-6822(83)90543-3. [DOI] [PubMed] [Google Scholar]
  26. Thompson R. L., Wagner E. K., Stevens J. G. Physical location of a herpes simplex virus type-1 gene function(s) specifically associated with a 10 million-fold increase in HSV neurovirulence. Virology. 1983 Nov;131(1):180–192. doi: 10.1016/0042-6822(83)90544-5. [DOI] [PubMed] [Google Scholar]
  27. Weiner H. L., Drayna D., Averill D. R., Jr, Fields B. N. Molecular basis of reovirus virulence: role of the S1 gene. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5744–5748. doi: 10.1073/pnas.74.12.5744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Závada V., Erban V., Rezácová D., Vonka V. Thymidine-kinase in cytomegalovirus infected cells. Arch Virol. 1976;52(4):333–339. doi: 10.1007/BF01315622. [DOI] [PubMed] [Google Scholar]

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