Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Aug;71(8):5820–5827. doi: 10.1128/jvi.71.8.5820-5827.1997

The gE and gI homologs from two alphaherpesviruses have conserved and divergent neuroinvasive properties.

A C Knapp 1, P J Husak 1, L W Enquist 1
PMCID: PMC191837  PMID: 9223471

Abstract

The membrane glycoproteins gE and gI are encoded by pseudorabies virus (PRV), a neurotropic, broad-host-range alphaherpesvirus of swine. PRV gE and gI are required for anterograde spread to a restricted set of retinorecipient neurons in the brain after infection of the rat retina. A related alphaherpesvirus, encoding gE and gI homologs, is called bovine herpesvirus 1.1 (BHV-1.1). BHV-1.1 is a respiratory pathogen of highly restricted host range and, in contrast to PRV, is unable to propagate in or cause disease in rodents. We have shown previously that the BHV-1.1 gE and gI proteins are capable of complementing the virulence functions of PRV gE and gI in a rodent model (A. C. Knapp and L. W. Enquist, J. Virol. 71:2731-2739, 1997). We examined the ability of the BHV-1.1 gE and gI homologs to direct circuit-specific invasion of the rat central nervous system by PRV. Both complete open reading frames were cloned into a PRV mutant lacking the PRV gE and gI genes. Recombinant viruses were analyzed for the ability to invade the rat brain after infection of the retina. Surprisingly, in a portion of the animals tested, the BHV-1.1 gE and gI proteins functioned autonomously to promote spread of PRV to a subset of retinorecipient regions of the brain. First, the presence of BHV-1.1 gI alone, but not PRV gI alone, promoted viral invasion of the optic tectum. Second, expression of BHV-1.1 gE alone facilitated PRV infection of a subset of neurons in the hippocampus not normally infected by PRV. When both BHV-1.1 proteins were expressed in a coinfection, all retinorecipient regions of the rat brain were infected. Therefore, depending on the viral source, homologs of gE and gI differentially affect spread between synaptically connected neurons in the rat.

Full Text

The Full Text of this article is available as a PDF (562.9 KB).

Selected References

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

  1. Babic N., Mettenleiter T. C., Ugolini G., Flamand A., Coulon P. Propagation of pseudorabies virus in the nervous system of the mouse after intranasal inoculation. Virology. 1994 Nov 1;204(2):616–625. doi: 10.1006/viro.1994.1576. [DOI] [PubMed] [Google Scholar]
  2. Balan P., Davis-Poynter N., Bell S., Atkinson H., Browne H., Minson T. An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ. J Gen Virol. 1994 Jun;75(Pt 6):1245–1258. doi: 10.1099/0022-1317-75-6-1245. [DOI] [PubMed] [Google Scholar]
  3. Card J. P., Rinaman L., Schwaber J. S., Miselis R. R., Whealy M. E., Robbins A. K., Enquist L. W. Neurotropic properties of pseudorabies virus: uptake and transneuronal passage in the rat central nervous system. J Neurosci. 1990 Jun;10(6):1974–1994. doi: 10.1523/JNEUROSCI.10-06-01974.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dingwell K. S., Brunetti C. R., Hendricks R. L., Tang Q., Tang M., Rainbow A. J., Johnson D. C. Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. J Virol. 1994 Feb;68(2):834–845. doi: 10.1128/jvi.68.2.834-845.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dingwell K. S., Doering L. C., Johnson D. C. Glycoproteins E and I facilitate neuron-to-neuron spread of herpes simplex virus. J Virol. 1995 Nov;69(11):7087–7098. doi: 10.1128/jvi.69.11.7087-7098.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dubin G., Basu S., Mallory D. L., Basu M., Tal-Singer R., Friedman H. M. Characterization of domains of herpes simplex virus type 1 glycoprotein E involved in Fc binding activity for immunoglobulin G aggregates. J Virol. 1994 Apr;68(4):2478–2485. doi: 10.1128/jvi.68.4.2478-2485.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Enquist L. W., Dubin J., Whealy M. E., Card J. P. Complementation analysis of pseudorabies virus gE and gI mutants in retinal ganglion cell neurotropism. J Virol. 1994 Aug;68(8):5275–5279. doi: 10.1128/jvi.68.8.5275-5279.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jacobs L. Glycoprotein E of pseudorabies virus and homologous proteins in other alphaherpesvirinae. Arch Virol. 1994;137(3-4):209–228. doi: 10.1007/BF01309470. [DOI] [PubMed] [Google Scholar]
  9. Kaashoek M. J., Moerman A., Madić J., Rijsewijk F. A., Quak J., Gielkens A. L., van Oirschot J. T. A conventionally attenuated glycoprotein E-negative strain of bovine herpesvirus type 1 is an efficacious and safe vaccine. Vaccine. 1994 Apr;12(5):439–444. doi: 10.1016/0264-410x(94)90122-8. [DOI] [PubMed] [Google Scholar]
  10. Knapp A. C., Enquist L. W. Pseudorabies virus recombinants expressing functional virulence determinants gE and gI from bovine herpesvirus 1.1. J Virol. 1997 Apr;71(4):2731–2739. doi: 10.1128/jvi.71.4.2731-2739.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kritas S. K., Nauwynck H. J., Pensaert M. B. Dissemination of wild-type and gC-, gE-and gI-deleted mutants of Aujeszky's disease virus in the maxillary nerve and trigeminal ganglion of pigs after intranasal inoculation. J Gen Virol. 1995 Aug;76(Pt 8):2063–2066. doi: 10.1099/0022-1317-76-8-2063. [DOI] [PubMed] [Google Scholar]
  12. Kritas S. K., Pensaert M. B., Mettenleiter T. C. Invasion and spread of single glycoprotein deleted mutants of Aujeszky's disease virus (ADV) in the trigeminal nervous pathway of pigs after intranasal inoculation. Vet Microbiol. 1994 Jun;40(3-4):323–334. doi: 10.1016/0378-1135(94)90120-1. [DOI] [PubMed] [Google Scholar]
  13. Kritas S. K., Pensaert M. B., Mettenleiter T. C. Role of envelope glycoproteins gI, gp63 and gIII in the invasion and spread of Aujeszky's disease virus in the olfactory nervous pathway of the pig. J Gen Virol. 1994 Sep;75(Pt 9):2319–2327. doi: 10.1099/0022-1317-75-9-2319. [DOI] [PubMed] [Google Scholar]
  14. Maidji E., Tugizov S., Jones T., Zheng Z., Pereira L. Accessory human cytomegalovirus glycoprotein US9 in the unique short component of the viral genome promotes cell-to-cell transmission of virus in polarized epithelial cells. J Virol. 1996 Dec;70(12):8402–8410. doi: 10.1128/jvi.70.12.8402-8410.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mulder W., Pol J., Kimman T., Kok G., Priem J., Peeters B. Glycoprotein D-negative pseudorabies virus can spread transneuronally via direct neuron-to-neuron transmission in its natural host, the pig, but not after additional inactivation of gE or gI. J Virol. 1996 Apr;70(4):2191–2200. doi: 10.1128/jvi.70.4.2191-2200.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Risold P. Y., Swanson L. W. Structural evidence for functional domains in the rat hippocampus. Science. 1996 Jun 7;272(5267):1484–1486. doi: 10.1126/science.272.5267.1484. [DOI] [PubMed] [Google Scholar]
  17. Wentink G. H., van Oirschot J. T., Verhoeff J. Risk of infection with bovine herpes virus 1 (BHV1): a review. Vet Q. 1993 Mar;15(1):30–33. doi: 10.1080/01652176.1993.9694365. [DOI] [PubMed] [Google Scholar]
  18. Whealy M. E., Card J. P., Robbins A. K., Dubin J. R., Rziha H. J., Enquist L. W. Specific pseudorabies virus infection of the rat visual system requires both gI and gp63 glycoproteins. J Virol. 1993 Jul;67(7):3786–3797. doi: 10.1128/jvi.67.7.3786-3797.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Whitbeck J. C., Knapp A. C., Enquist L. W., Lawrence W. C., Bello L. J. Synthesis, processing, and oligomerization of bovine herpesvirus 1 gE and gI membrane proteins. J Virol. 1996 Nov;70(11):7878–7884. doi: 10.1128/jvi.70.11.7878-7884.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yao Z., Jackson W., Forghani B., Grose C. Varicella-zoster virus glycoprotein gpI/gpIV receptor: expression, complex formation, and antigenicity within the vaccinia virus-T7 RNA polymerase transfection system. J Virol. 1993 Jan;67(1):305–314. doi: 10.1128/jvi.67.1.305-314.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zuckermann F. A., Mettenleiter T. C., Schreurs C., Sugg N., Ben-Porat T. Complex between glycoproteins gI and gp63 of pseudorabies virus: its effect on virus replication. J Virol. 1988 Dec;62(12):4622–4626. doi: 10.1128/jvi.62.12.4622-4626.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. van Engelenburg F. A., Kaashoek M. J., van Oirschot J. T., Rijsewijk F. A. A glycoprotein E deletion mutant of bovine herpesvirus 1 infects the same limited number of tissues in calves as wild-type virus, but for a shorter period. J Gen Virol. 1995 Sep;76(Pt 9):2387–2392. doi: 10.1099/0022-1317-76-9-2387. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES