Skip to main content
PMC home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2004 Dec 7;6(1):41–49. doi: 10.1016/0890-8508(92)90070-E

Mapping neuroinvasiveness of the herpes simplex virus type 1 encephalitis-inducing strain 2762 by the use of monoclonal antibodies

T Bergström 1,∗, E Sjögren-Jansson 1, S Jeansson 1, E Lycke 1
PMCID: PMC7135814  PMID: 1312221

Abstract

Monoclonal antibodies (MAbs) directed against herpes simplex virus (HSV)-coded glycoproteins gB, gC, gD and gE were employed in an in vitro model of neuroinvasiveness using sensory neurons from rat dorsal root ganglion (DRG) cells. The neurons were cultured in a two-chamber system allowing infection via the neuritic extensions exclusively. The effects of 30 MAbs on viral replication of the encephalitis-derived HSV-1 strain 2762 and its less neuroinvasive variant 2762p11 were assayed in this model. One MAb reactive with gD gave a nine-fold reduction of the virus yields of both strains. One MAb directed against gB gave an enhanced virus yield of strain 2762, but not of the 2762p11 variant. Another gB-reactive MAb decreased the virus yield of strain 2762p11, but not of 2762 after neuritic infection. The findings indicate that an alteration of gB has occurred during the passage of the strain 2762. Mutants of the same strain were derived by infecting hybridomas producing MAb reactive with gB, gC, gD and gE, respectively. The gB hybridoma mutant showed a significantly lower neuroinvasiveness in the DRG model, and was non-virulent after snout infection of mice. We suggest that the structure of gB of the strain 2762 is of importance for the neuroinvasiveness of this strain.

Keywords: HSV-1, encephalitis, neuroinvasiveness, monoclonal antibodies, hybridoma mutants

References

  • 1.Whitley R.J. Viral encephalitis. New England Journal of Medicine. 1990;323:242–250. doi: 10.1056/NEJM199007263230406. [DOI] [PubMed] [Google Scholar]
  • 2.Sköldenberg B., Forsgren M., Alestig K. Acyclovir versus Vidarabine in herpes simplex encephalitis. Lancet. 1984;ii:707–711. doi: 10.1016/s0140-6736(84)92623-0. [DOI] [PubMed] [Google Scholar]
  • 3.Whitley R.J., Lakeman A.D., Nahmias A., Roizman B. DNA restriction enzyme analysis of herpes simplex virus isolates obtained from patients with encephalitis. New England Journal of Medicine. 1982;307:1060–1062. doi: 10.1056/NEJM198210213071706. [DOI] [PubMed] [Google Scholar]
  • 4.Meigner B., Longnecker R., Mavromara-Nazos P., Sears A.E., Roizman B. Virulence of and establishment of latency by genetically engineered deletion mutants of herpes simplex virus 1. Virology. 1988;162:251–254. doi: 10.1016/0042-6822(88)90417-5. [DOI] [PubMed] [Google Scholar]
  • 5.Chou J., Kern E.R., Whitley R.J., Roizman B. Mapping of herpes simplex virus-1 neurovirulence to τ134·5, a gene nonessential for growth in culture. Science. 1990;250:1262–1266. doi: 10.1126/science.2173860. [DOI] [PubMed] [Google Scholar]
  • 6.Javier R.T., Thompson R.L., Stevens J.G. Genetic and biological analysis of a herpes simplex virus intertypic recombinant reduced specifically for neurovirulence. Journal of Virology. 1987;61:1978–1984. doi: 10.1128/jvi.61.6.1978-1984.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Thompson R.L., Rogers S.K., Zerhusen M.A. Herpes simplex virus neurovirulence and productive infection of neural cells is associated with a function which maps between 0·82 and 0·832 map units of the HSV genome. Virology. 1989;172:435–450. doi: 10.1016/0042-6822(89)90186-4. [DOI] [PubMed] [Google Scholar]
  • 8.Dix R.D., McKendall R.R., Baringer R.J. Comparative neurovirulence of herpes simplex virus type 1 strains after peripheral or intracerebral inoculation of BALB/c mice. Infection and Immunity. 1983;40:103–112. doi: 10.1128/iai.40.1.103-112.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Richards J.T., Kern E.R., Overall J.C., Jr, Glasgow L.A. Differences in neurovirulence among isolates of herpes simplex virus types 1 and 2 in mice using four routes of infection. Journal of Infectious Diseases. 1981;144:464–471. doi: 10.1093/infdis/144.5.464. [DOI] [PubMed] [Google Scholar]
  • 10.Bergström T., Lycke E. Neuroinvasion by herpes simplex virus. An in vitro model for characterization of neurovirulent strains. Journal of General Virology. 1990;71:405–410. doi: 10.1099/0022-1317-71-2-405. [DOI] [PubMed] [Google Scholar]
  • 11.Bergström T., Alestig K., Svennerholm B., Horal P., Sköldenberg B., Vahlne A. Neurovirulence of herpes simplex virus types 1 and 2 isolates in diseases of the central nervous system. European Journal of Clinical Microbiology and Infectious Diseases. 1990;9:751–757. doi: 10.1007/BF02184688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Highlander S.L., Dorney D.J., Gage P.J., Holland T.C., Cai W., Person S., Levine M., Glorioso J.C. Identification of mar mutations in herpes simplex virus type 1 glycoprotein B which alter antigenic structure and function in virus penetration. Journal of Virology. 1989;63:730–738. doi: 10.1128/jvi.63.2.730-738.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kühn J.E., Kramer M.D., Willenbacher W., Wieland U., Lorentzon E.U., Braun R.W. Identification of herpes simplex virus type 1 glycoproteins interacting with the cell surface. Journal of Virology. 1990;64:2491–2497. doi: 10.1128/jvi.64.6.2491-2497.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Fuller O., Spear P.G. 2nd edn. Vol. 84. 1987. Anti-glycoprotein D antibodies that permit adsorption but block infection by herpes simplex virus type 1 prevent virion-cell fusion at the surface; pp. 5454–5458. (Proceedings of the National Academy of Sciences, USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Chatterjee S., Koga J., Whitley R.J. A role for herpes simplex virus type 1 glycoprotein E in induction of cell fusion. Journal of General Virology. 1989;70:2157–2162. doi: 10.1099/0022-1317-70-8-2157. [DOI] [PubMed] [Google Scholar]
  • 16.Svennerholm B., Jeansson S., Vahlne A., Lycke E. Involvement of glycoprotein C (gC) in adsorption of herpes simplex virus type 1 (HSV-1) to the cell. Archives of Virology. 1991 doi: 10.1007/BF01310482. (in press) [DOI] [PubMed] [Google Scholar]
  • 17.Nilheden E., Jeansson S., Vahlne A. Typing of herpes simplex virus by an enzyme-linked immunoassay with monoclonal antibodies. Journal of Clinical Microbiology. 1983;17:677–680. doi: 10.1128/jcm.17.4.677-680.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Fazekas G.S., Scheidegger D. Production of monoclonal antibodies: strategy and tactics. Journal of Immunological Methods. 1980;35:1–21. doi: 10.1016/0022-1759(80)90146-5. [DOI] [PubMed] [Google Scholar]
  • 19.Jeansson S., Forsgren M., Svennerholm B. Evaluation of solubilized herpes simplex virus membrane antigen by enzyme-linked immunosorbent assay. Journal of Clinical Microbiology. 1983;18:1160–1166. doi: 10.1128/jcm.18.5.1160-1166.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Mancini G.J., Vaerman I.P., Carbonera A.O., Heremans J.F. Protides of the Biological Fluids. In: Peeters H., editor. XI Colloquium; Bruges 1963; Amsterdam: Elsevier; 1964. p. 370. [Google Scholar]
  • 21.Sjögren-Jansson E., Jeansson S. Large-scale production of monoclonal antibodies in dialysis tubing. Journal of Immunological Methods. 1985;84:359–364. doi: 10.1016/0022-1759(85)90442-9. [DOI] [PubMed] [Google Scholar]
  • 22.Sjögren-Jansson E., Jeansson S. Growing hybridomas in dialysis tubing: Optimization of the technique. In: Zola H., editor. 2nd edn. Vol. 1. CRC Press, Inc; Boca Raton: 1990. pp. 41–50. (Laboratory Methods in Immunology). [Google Scholar]
  • 23.Olofsson S., Sjöblom I., Lundström M., Jeansson S., Lycke E. Glycoprotein C of herpes simplex virus type 1: Characterization of O-linked oligosaccharides. Journal of General Virology. 1983;64:2735–2747. doi: 10.1099/0022-1317-64-12-2735. [DOI] [PubMed] [Google Scholar]
  • 24.Morse L.S., Pereira L., Roizman B., Schaffer P.A. Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 × HSV-2 recombinants. Journal of Virology. 1978;26:389–410. doi: 10.1128/jvi.26.2.389-410.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Wege H., Winter J., Meyermann R. The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: Definition of critical epitopes by variant analysis. Journal of General Virology. 1988;69:87–98. doi: 10.1099/0022-1317-69-1-87. [DOI] [PubMed] [Google Scholar]
  • 26.Campenot R.B. 2nd edn. Vol. 74. 1977. Local control of neurite development by nerve growth factor; pp. 4516–4518. (Proceedings of the National Academy of Sciences, USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Lycke E., Kristensson K., Svennerholm B., Vahlne A., Ziegler R. Uptake and transport of herpes simplex virus in neuntes of rat dorsal root ganglia cells in culture. Journal of General Virology. 1984;65:55–64. doi: 10.1099/0022-1317-65-1-55. [DOI] [PubMed] [Google Scholar]
  • 28.Rajcáni J., Herget U., Kaerner H.C. Spread of herpes simplex virus (HSV) strains SC16, ANG, ANG-path, and its glyC minus and glyE minus mutants in DBA-2 mice. Acta Virologica. 1990;34:305–320. [PubMed] [Google Scholar]
  • 29.Holzmann H., Heinz F.X., Mandl C.W., Guirakhoo F., Kunz F. A single amino acid substitution in envelope protein E of tick-borne encephalitis virus leads to attenuation in the mouse model. Journal of Virology. 1990;64:5156–5159. doi: 10.1128/jvi.64.10.5156-5159.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Weise K., Kaerner H.C., Glorioso J., Schröder C.H. Replacement of glycoprotein B sequences in herpes simplex virus type 1 strain ANG by corresponding sequences of the strain KOS causes changes of plaque morphology and neuropathogenicity. Journal of General Virology. 1987;68:1909–1919. doi: 10.1099/0022-1317-68-7-1909. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Probes are provided here courtesy of Elsevier

RESOURCES