Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1980 Jul;35(1):203–210. doi: 10.1128/jvi.35.1.203-210.1980

Persistence of herpes simplex virus genes in cells of neuronal origin.

M Levine, A L Goldin, J C Glorioso
PMCID: PMC288796  PMID: 6251268

Abstract

The growth characteristics of the KOS strain of herpes simplex virus type 1 (HSV-1) in cell lines of nervous tissues origin were examined in an attempt to develop a tissue culture system mimicking the in vivo state of HSV-1 latency. We have previously reported that the B103 rat brain neuroma cell line is nonpermissive for growth of the KOS strain. In this report, we show that this nonpermissiveness is a temperature- and multiplicity-dependent phenomenon, with minimum virus yields at an elevated temperature and a low multiplicity of infection. Under these conditions, B103 cells survived infection with active wild-type or mutant HSV-1, whereas similarly treated Vero cells were killed. Six independent cultures of B103 cells surviving HSV-1 infection have been established. The surviving cells ceased production of any HSV-1 virus by 14 days postinfection and resumed growth and division at rates comparable to those of uninfected B103 cells. Survivor cells continued to express HSV-1-specific antigens, however, as detected by indirect immunofluorescence and by surface iodination followed by immunoprecipitation and polyacrylamide gel electrophoresis. The survivor cells did not express all of the surface proteins seen on productively infected B103 cells, and they were not susceptible to complement-mediated immune cytolysis with anti-HSV-1 antiserum. These results demonstrate that at least a portion of the HSV-1 genome is being harbored in these survivor cells.

Full text

PDF
203

Images in this article

Selected References

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

  1. Adler R., Glorioso J. C., Levine M. Infection by herpes simplex virus and cells of nervous system origin: characterization of a non-permissive interaction. J Gen Virol. 1978 Apr;39(1):9–20. doi: 10.1099/0022-1317-39-1-9. [DOI] [PubMed] [Google Scholar]
  2. Baringer J. R., Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med. 1973 Mar 29;288(13):648–650. doi: 10.1056/NEJM197303292881303. [DOI] [PubMed] [Google Scholar]
  3. Brown S. M., Subak-Sharpe J. H., Warren K. G., Wroblewska Z., Koprowski H. Detection by complementation of defective or uninducible (herpes simplex type 1) virus genomes latent in human ganglia. Proc Natl Acad Sci U S A. 1979 May;76(5):2364–2368. doi: 10.1073/pnas.76.5.2364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colberg-Poley A. M., Isom H. C., Rapp F. Reactivation of herpes simplex virus type 2 from a quiescent state by human cytomegalovirus. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5948–5951. doi: 10.1073/pnas.76.11.5948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cook M. L., Bastone V. B., Stevens J. G. Evidence that neurons harbor latent herpes simplex virus. Infect Immun. 1974 May;9(5):946–951. doi: 10.1128/iai.9.5.946-951.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cook M. L., Stevens J. G. Latent herpetic infections following experimental viraemia. J Gen Virol. 1976 Apr;31(1):75–80. doi: 10.1099/0022-1317-31-1-75. [DOI] [PubMed] [Google Scholar]
  7. Doller E., Aucker J., Weissbach A. Persistence of herpes simplex virus type 1 in rat neurotumor cells. J Virol. 1979 Jan;29(1):43–50. doi: 10.1128/jvi.29.1.43-50.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Galloway D. A., Fenoglio C., Shevchuk M., McDougall J. K. Detection of herpes simplex RNA in human sensory ganglia. Virology. 1979 May;95(1):265–268. doi: 10.1016/0042-6822(79)90429-x. [DOI] [PubMed] [Google Scholar]
  9. Gerdes J. C., Marsden H. S., Cook M. L., Stevens J. G. Acute infection of differentiated neuroblastoma cells by latency-positive and latency-negative herpes simplex virus ts mutants. Virology. 1979 Apr 30;94(2):430–441. doi: 10.1016/0042-6822(79)90473-2. [DOI] [PubMed] [Google Scholar]
  10. Glorioso J. C., Smith J. W. Immune interactions with cells infected with herpes simplex virus: antibodies to radioiodinated surface antigens. J Immunol. 1977 Jan;118(1):114–121. [PubMed] [Google Scholar]
  11. Glorioso J. C., Wilson L. A., Fenger T. W., Smith J. W. Complement-mediated cytolysis of HSV-1 and HSV-2 infected cells: plasma membrane antigens reactive with type-specific and cross-reactive antibody. J Gen Virol. 1978 Aug;40(2):443–454. doi: 10.1099/0022-1317-40-2-443. [DOI] [PubMed] [Google Scholar]
  12. Hampar B., Burroughs M. A. Mechanism of persistent herpes simplex virus infection in vitro. J Natl Cancer Inst. 1969 Sep;43(3):621–634. [PubMed] [Google Scholar]
  13. Hampar B., Copeland M. L. Persistent Herpes Simplex Virus Infection In Vitro with Cycles of Cell Destruction and Regrowth. J Bacteriol. 1965 Jul;90(1):205–212. doi: 10.1128/jb.90.1.205-212.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hughes R. G., Jr, Munyon W. H. Temperature-sensitive mutants of herpes simplex virus type 1 defective in lysis but not in transformation. J Virol. 1975 Aug;16(2):275–283. doi: 10.1128/jvi.16.2.275-283.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knotts F. B., Cook M. L., Stevens J. G. Latent herpes simplex virus in the central nervous system of rabbits and mice. J Exp Med. 1973 Sep 1;138(3):740–744. doi: 10.1084/jem.138.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  17. Lancz G. J., Zettlemoyer T. L. Restricted replication of herpes simplex virus in neural cells. Proc Soc Exp Biol Med. 1976 Jul;152(3):302–306. doi: 10.3181/00379727-152-39384. [DOI] [PubMed] [Google Scholar]
  18. Lofgren K. W., Stevens J. G., Marsden H. S., Subak-Sharpe J. H. Temperature-sensitive mutants of herpes simplex virus differ in the capacity to establish latent infections in mice. Virology. 1977 Jan;76(1):440–443. doi: 10.1016/0042-6822(77)90319-1. [DOI] [PubMed] [Google Scholar]
  19. Nii S. Persistent infection with herpes simplex virus in vitro. 1. Establishment and characteristics of persistent herpes simplex virus infection in Earle's L cells. Biken J. 1969 Jun;12(2):45–67. [PubMed] [Google Scholar]
  20. O'Neill F. J., Goldberg R. J., Rapp F. Herpes simplex virus latency in cultured human cells following treatment with cytosine arabinoside. J Gen Virol. 1972 Feb;14(2):189–197. doi: 10.1099/0022-1317-14-2-189. [DOI] [PubMed] [Google Scholar]
  21. O'Neill F. J. Prolongation of herpes simplex virus latency in cultured human cells by temperature elevation. J Virol. 1977 Oct;24(1):41–46. doi: 10.1128/jvi.24.1.41-46.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Puga A., Rosenthal J. D., Openshaw H., Notkins A. L. Herpes simplex virus DNA and mRNA sequences in acutely and chronically infected trigeminal ganglia of mice. Virology. 1978 Aug;89(1):102–111. doi: 10.1016/0042-6822(78)90044-2. [DOI] [PubMed] [Google Scholar]
  23. Rohrschneider L. R. Immunofluorescence on avian sarcoma virus-transformed cells: localization of the src gene product. Cell. 1979 Jan;16(1):11–24. doi: 10.1016/0092-8674(79)90183-1. [DOI] [PubMed] [Google Scholar]
  24. Schaffer P. A., Carter V. C., Timbury M. C. Collaborative complementation study of temperature-sensitive mutants of herpes simplex virus types 1 and 2. J Virol. 1978 Sep;27(3):490–504. doi: 10.1128/jvi.27.3.490-504.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schubert D., Heinemann S., Carlisle W., Tarikas H., Kimes B., Patrick J., Steinbach J. H., Culp W., Brandt B. L. Clonal cell lines from the rat central nervous system. Nature. 1974 May 17;249(454):224–227. doi: 10.1038/249224a0. [DOI] [PubMed] [Google Scholar]
  26. Smith J. W., Glorioso J. C. Effect of cross-immunization on monotypic antibody responses to herpes simplex virus types 1 and 2. J Immunol. 1976 Apr;116(4):898–903. [PubMed] [Google Scholar]
  27. 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]
  28. Stallcup W. B., Cohn M. Correlation of surface antigens and cell type in cloned cell lines from the rat central nervous system. Exp Cell Res. 1976 Mar 15;98(2):285–297. doi: 10.1016/0014-4827(76)90440-7. [DOI] [PubMed] [Google Scholar]
  29. Stevens J. G., Cook M. L. Latent herpes simplex virus in spinal ganglia of mice. Science. 1971 Aug 27;173(3999):843–845. doi: 10.1126/science.173.3999.843. [DOI] [PubMed] [Google Scholar]
  30. Stevens J. G. Latent herpes simplex virus and the nervous system,. Curr Top Microbiol Immunol. 1975;70:31–50. doi: 10.1007/978-3-642-66101-3_2. [DOI] [PubMed] [Google Scholar]
  31. Stevens J. G., Nesburn A. B., Cook M. L. Latent herpes simplex virus from trigeminal ganglia of rabbits with recurrent eye infection. Nat New Biol. 1972 Feb 16;235(59):216–217. doi: 10.1038/newbio235216a0. [DOI] [PubMed] [Google Scholar]
  32. Vahlne A., Lycke E. Herpes simplex virus infection of in vitro cultured neuronal cells (mouse neuroblastoma C 1300 cells). J Gen Virol. 1978 May;39(2):321–332. doi: 10.1099/0022-1317-39-2-321. [DOI] [PubMed] [Google Scholar]
  33. Vahlne A., Lycke E. Herpes simplex virus infection of mouse neuroblastoma cells (39880). Proc Soc Exp Biol Med. 1977 Oct;156(1):82–87. doi: 10.3181/00379727-156-39880. [DOI] [PubMed] [Google Scholar]
  34. Walz M. A., Price R. W., Notkins A. L. Latent ganglionic infection with herpes simplex virus types 1 and 2: viral reactivation in vivo after neurectomy. Science. 1974 Jun 14;184(4142):1185–1187. doi: 10.1126/science.184.4142.1185. [DOI] [PubMed] [Google Scholar]

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

RESOURCES