Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1988 Feb;62(2):393–399. doi: 10.1128/jvi.62.2.393-399.1988

Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro.

C L Wilcox 1, E M Johnson Jr 1
PMCID: PMC250548  PMID: 2826804

Abstract

Primary sympathetic neuronal cultures were maintained for up to 5 weeks after inoculation with herpes simplex virus (HSV) without evidence of viral infection. Treatment with acyclovir for the first 7 days after viral inoculation prevented lytic infections in 100% of the cultures and resulted in viral latency in 100% of the cultures; reactivation occurred as the result of nerve growth factor (NGF) deprivation. Treatment of the cultures with several different inhibitors of viral DNA polymerase (acyclovir, aphidicolin, and phosphonoacetic acid) for 7 days after viral inoculation did not prevent the establishment of latency, which suggests that viral DNA replication was not required. During the latent phase of the infection, viral antigens were not detected with HSV-specific immunohistochemistry. However, 24 h after NGF deprivation, viral antigens were detected in essentially all of the neurons, indicating that the majority of neurons harbored latent HSV. The establishment of latency was not strain or type specific since latency was established with HSV type 2 and four strains of HSV type 1 and reactivation occurred in response to NGF deprivation.

Full text

PDF
393

Images in this article

396Image
on p.396
397Image
on p.397

Selected References

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

  1. 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]
  2. Bastian F. O., Rabson A. S., Yee C. L., Tralka T. S. Herpesvirus hominis: isolation from human trigeminal ganglion. Science. 1972 Oct 20;178(4058):306–307. doi: 10.1126/science.178.4058.306. [DOI] [PubMed] [Google Scholar]
  3. Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bocchini V., Angeletti P. U. The nerve growth factor: purification as a 30,000-molecular-weight protein. Proc Natl Acad Sci U S A. 1969 Oct;64(2):787–794. doi: 10.1073/pnas.64.2.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CARTON C. A., KILBOURNE E. D. Activation of latent herpes simplex by trigeminal sensory-root section. N Engl J Med. 1952 Jan 31;246(5):172–176. doi: 10.1056/NEJM195201312460503. [DOI] [PubMed] [Google Scholar]
  6. Deatly A. M., Spivack J. G., Lavi E., Fraser N. W. RNA from an immediate early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice. Proc Natl Acad Sci U S A. 1987 May;84(10):3204–3208. doi: 10.1073/pnas.84.10.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elion G. B., Furman P. A., Fyfe J. A., de Miranda P., Beauchamp L., Schaeffer H. J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5716–5720. doi: 10.1073/pnas.74.12.5716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fenton E. L. Tissue culture assay of nerve growth factor and of the specific antiserum. Exp Cell Res. 1970 Mar;59(3):383–392. doi: 10.1016/0014-4827(70)90645-2. [DOI] [PubMed] [Google Scholar]
  9. Fenwick M. L., Clark J. Early and delayed shut-off of host protein synthesis in cells infected with herpes simplex virus. J Gen Virol. 1982 Jul;61(Pt 50):121–125. doi: 10.1099/0022-1317-61-1-121. [DOI] [PubMed] [Google Scholar]
  10. Green M. T., Courtney R. J., Dunkel E. C. Detection of an immediate early herpes simplex virus type 1 polypeptide in trigeminal ganglia from latently infected animals. Infect Immun. 1981 Dec;34(3):987–992. doi: 10.1128/iai.34.3.987-992.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hendry I. A., Stöckel K., Thoenen H., Iversen L. L. The retrograde axonal transport of nerve growth factor. Brain Res. 1974 Mar 15;68(1):103–121. doi: 10.1016/0006-8993(74)90536-8. [DOI] [PubMed] [Google Scholar]
  12. Honess R. W., Purifoy D. J., Young D., Gopal R., Cammack N., O'Hare P. Single mutations at many sites within the DNA polymerase locus of herpes simplex viruses can confer hypersensitivity to aphidicolin and resistance to phosphonoacetic acid. J Gen Virol. 1984 Jan;65(Pt 1):1–17. doi: 10.1099/0022-1317-65-1-1. [DOI] [PubMed] [Google Scholar]
  13. Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson E. M., Jr, Yip H. K. Central nervous system and peripheral nerve growth factor provide trophic support critical to mature sensory neuronal survival. 1985 Apr 25-May 1Nature. 314(6013):751–752. doi: 10.1038/314751a0. [DOI] [PubMed] [Google Scholar]
  15. Johnson M. I., Argiro V. Techniques in the tissue culture of rat sympathetic neurons. Methods Enzymol. 1983;103:334–347. doi: 10.1016/s0076-6879(83)03022-0. [DOI] [PubMed] [Google Scholar]
  16. Kennedy P. G., Al-Saadi S. A., Clements G. B. Reactivation of latent herpes simplex virus from dissociated identified dorsal root ganglion cells in culture. J Gen Virol. 1983 Jul;64(Pt 7):1629–1635. doi: 10.1099/0022-1317-64-7-1629. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. McLennan J. L., Darby G. Herpes simplex virus latency: the cellular location of virus in dorsal root ganglia and the fate of the infected cell following virus activation. J Gen Virol. 1980 Dec;51(Pt 2):233–243. doi: 10.1099/0022-1317-51-2-233. [DOI] [PubMed] [Google Scholar]
  19. Murchie M. J., McGeoch D. J. DNA sequence analysis of an immediate-early gene region of the herpes simplex virus type 1 genome (map coordinates 0.950 to 0.978). J Gen Virol. 1982 Sep;62(Pt 1):1–15. doi: 10.1099/0022-1317-62-1-1. [DOI] [PubMed] [Google Scholar]
  20. Nishioka Y., Silverstein S. Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1. J Virol. 1978 Sep;27(3):619–627. doi: 10.1128/jvi.27.3.619-627.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Njå A., Purves D. The effects of nerve growth factor and its antiserum on synapses in the superior cervical ganglion of the guinea-pig. J Physiol. 1978 Apr;277:53–75. [PMC free article] [PubMed] [Google Scholar]
  22. Plummer G. Isolation of herpesviruses from trigeminal ganglia of man, monkeys, and cats. J Infect Dis. 1973 Sep;128(3):345–347. doi: 10.1093/infdis/128.3.345. [DOI] [PubMed] [Google Scholar]
  23. Post L. E., Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. Cell. 1981 May;24(2):555–565. doi: 10.1016/0092-8674(81)90346-9. [DOI] [PubMed] [Google Scholar]
  24. Price R. W., Katz B. J., Notkins A. L. Latent infection of the peripheral ANS with herpes simplex virus. Nature. 1975 Oct 23;257(5528):686–688. doi: 10.1038/257686a0. [DOI] [PubMed] [Google Scholar]
  25. Price R. W., Schmitz J. Reactivation of latent herpes simplex virus infection of the autonomic nervous system by postganglionic neurectomy. Infect Immun. 1978 Feb;19(2):523–532. doi: 10.1128/iai.19.2.523-532.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Puga A., Notkins A. L. Continued expression of a poly(A)+ transcript of herpes simplex virus type 1 in trigeminal ganglia of latently infected mice. J Virol. 1987 May;61(5):1700–1703. doi: 10.1128/jvi.61.5.1700-1703.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Purves D., Njå A. Effect of nerve growth factor on synaptic depression after axotomy. Nature. 1976 Apr 8;260(5551):535–536. doi: 10.1038/260535a0. [DOI] [PubMed] [Google Scholar]
  28. Rich K. M., Yip H. K., Osborne P. A., Schmidt R. E., Johnson E. M., Jr Role of nerve growth factor in the adult dorsal root ganglia neuron and its response to injury. J Comp Neurol. 1984 Nov 20;230(1):110–118. doi: 10.1002/cne.902300110. [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 characteristics of selected herpesviruses. Adv Cancer Res. 1978;26:227–256. doi: 10.1016/s0065-230x(08)60089-5. [DOI] [PubMed] [Google Scholar]
  31. Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., Feldman L. T. RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science. 1987 Feb 27;235(4792):1056–1059. doi: 10.1126/science.2434993. [DOI] [PubMed] [Google Scholar]
  32. Thoenen H., Barde Y. A. Physiology of nerve growth factor. Physiol Rev. 1980 Oct;60(4):1284–1335. doi: 10.1152/physrev.1980.60.4.1284. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Warren K. G., Brown S. M., Wroblewska Z., Gilden D., Koprowski H., Subak-Sharpe J. Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings. N Engl J Med. 1978 May 11;298(19):1068–1069. doi: 10.1056/NEJM197805112981907. [DOI] [PubMed] [Google Scholar]
  35. Watson K., Stevens J. G., Cook M. L., Subak-Sharpe J. H. Latency competence of thirteen HSV-1 temperature-sensitive mutants. J Gen Virol. 1980 Jul;49(1):149–159. doi: 10.1099/0022-1317-49-1-149. [DOI] [PubMed] [Google Scholar]
  36. Wilcox C. L., Johnson E. M., Jr Nerve growth factor deprivation results in the reactivation of latent herpes simplex virus in vitro. J Virol. 1987 Jul;61(7):2311–2315. doi: 10.1128/jvi.61.7.2311-2315.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES