Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1987 Dec;61(12):3820–3826. doi: 10.1128/jvi.61.12.3820-3826.1987

Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1.

D L Rock 1, A B Nesburn 1, H Ghiasi 1, J Ong 1, T L Lewis 1, J R Lokensgard 1, S L Wechsler 1
PMCID: PMC255998  PMID: 2824816

Abstract

Using a combination of in situ hybridization and Northern (RNA) blot analysis, we investigated herpes simplex virus type 1 (HSV-1) transcriptional activity in an ocular rabbit model of HSV-1 latency. Radioactively labeled cloned fragments, representing virtually the entire HSV-1 genome, were individually hybridized to RNA in sections of trigeminal ganglia taken from rabbits during the latent phase of infection with HSV-1 (McKrae). Our results suggest that two discrete latency-related RNAs (LR-RNAs) may be present. The LR-RNAs were localized mainly in the nuclei of neurons. The more abundant LR-RNA was detected in approximately 3% of all neurons examined and was designated major LR-RNA. The other LR-RNA, designated minor LR-RNA, was detected in approximately 0.3% of neurons from latently infected rabbits. The genes for the LR-RNAs mapped in the vicinity of the immediate-early gene ICP0 (also designated IE110). The gene for the major LR-RNA partially overlapped the left (3') end of the ICP0 gene. In situ hybridization with single-stranded RNA probes showed that this LR-RNA was of complementary sense to that of ICP0 mRNA. Northern blot analysis gave an approximate size for this LR-RNA of 1.8 to 2.2 kilobases. The minor LR-RNA mapped to or near the right (5') end of the ICP0 gene. The detection of LR-RNAs suggests the possibility that these RNAs or their products may play significant roles in the initiation and/or maintenance of HSV-1 latency.

Full text

PDF
3820

Images in this article

Selected References

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

  1. Cabrera C. V., Wohlenberg C., Openshaw H., Rey-Mendez M., Puga A., Notkins A. L. Herpes simplex virus DNA sequences in the CNS of latently infected mice. Nature. 1980 Nov 20;288(5788):288–290. doi: 10.1038/288288a0. [DOI] [PubMed] [Google Scholar]
  2. Chang T. W. Recurrent viral infection (reinfection). N Engl J Med. 1971 Apr 8;284(14):765–773. doi: 10.1056/NEJM197104082841406. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Fraser N. W., Lawrence W. C., Wroblewska Z., Gilden D. H., Koprowski H. Herpes simplex type 1 DNA in human brain tissue. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6461–6465. doi: 10.1073/pnas.78.10.6461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Galloway D. A., Fenoglio C. M., McDougall J. K. Limited transcription of the herpes simplex virus genome when latent in human sensory ganglia. J Virol. 1982 Feb;41(2):686–691. doi: 10.1128/jvi.41.2.686-691.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Goldin A. L., Sandri-Goldin R. M., Levine M., Glorioso J. C. Cloning of herpes simplex virus type 1 sequences representing the whole genome. J Virol. 1981 Apr;38(1):50–58. doi: 10.1128/jvi.38.1.50-58.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Green P. J., Pines O., Inouye M. The role of antisense RNA in gene regulation. Annu Rev Biochem. 1986;55:569–597. doi: 10.1146/annurev.bi.55.070186.003033. [DOI] [PubMed] [Google Scholar]
  10. Kim S. K., Wold B. J. Stable reduction of thymidine kinase activity in cells expressing high levels of anti-sense RNA. Cell. 1985 Aug;42(1):129–138. doi: 10.1016/s0092-8674(85)80108-2. [DOI] [PubMed] [Google Scholar]
  11. Laibson P. R. Cornea and sclera. Arch Ophthalmol. 1970 May;83(5):637–657. doi: 10.1001/archopht.1970.00990030637021. [DOI] [PubMed] [Google Scholar]
  12. Nesburn A. B., Cook M. L., Stevens J. G. Latent herpes simplex virus. Isolation from rabbit trigeminal ganglia between episodes of recurrent ocular infection. Arch Ophthalmol. 1972 Oct;88(4):412–417. doi: 10.1001/archopht.1972.01000030414012. [DOI] [PubMed] [Google Scholar]
  13. Nesburn A. B., Dickinson R., Radnoti M., Green M. J. Experimental reactivation of ocular herpes simplex in rabbits. Surv Ophthalmol. 1976 Sep-Oct;21(2):185–190. doi: 10.1016/0039-6257(76)90098-9. [DOI] [PubMed] [Google Scholar]
  14. Nesburn A. B., Dunkel E. D., Trousdale M. D. Enhanced HSV recovery from neuronal tissues of latently infected rabbit. Proc Soc Exp Biol Med. 1980 Mar;163(3):398–401. doi: 10.3181/00379727-163-40785. [DOI] [PubMed] [Google Scholar]
  15. Nesburn A. B., Elliott J. H., Leibowitz H. M. Spontaneous reactivation of experimental herpes simplex keratitis in rabbits. Arch Ophthalmol. 1967 Oct;78(4):523–529. doi: 10.1001/archopht.1967.00980030525021. [DOI] [PubMed] [Google Scholar]
  16. PAINE T. F., Jr LATENT HERPES SIMPLEX INFECTION IN MAN. Bacteriol Rev. 1964 Dec;28:472–479. doi: 10.1128/br.28.4.472-479.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Perry L. J., Rixon F. J., Everett R. D., Frame M. C., McGeoch D. J. Characterization of the IE110 gene of herpes simplex virus type 1. J Gen Virol. 1986 Nov;67(Pt 11):2365–2380. doi: 10.1099/0022-1317-67-11-2365. [DOI] [PubMed] [Google Scholar]
  18. Post L. E., Conley A. J., Mocarski E. S., Roizman B. Cloning of reiterated and nonreiterated herpes simplex virus 1 sequences as BamHI fragments. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4201–4205. doi: 10.1073/pnas.77.7.4201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Rock D. L., Fraser N. W. Detection of HSV-1 genome in central nervous system of latently infected mice. Nature. 1983 Apr 7;302(5908):523–525. doi: 10.1038/302523a0. [DOI] [PubMed] [Google Scholar]
  22. Rock D. L., Fraser N. W. Latent herpes simplex virus type 1 DNA contains two copies of the virion DNA joint region. J Virol. 1985 Sep;55(3):849–852. doi: 10.1128/jvi.55.3.849-852.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rock D. L., Hagemoser W. A., Osorio F. A., Reed D. E. Detection of bovine herpesvirus type 1 RNA in trigeminal ganglia of latently infected rabbits by in situ hybridization. J Gen Virol. 1986 Nov;67(Pt 11):2515–2520. doi: 10.1099/0022-1317-67-11-2515. [DOI] [PubMed] [Google Scholar]
  24. SCOTT T. F., TOKUMARU T. HERPESVIRUS HOMINIS (VIRUS OF HERPES SIMPLEX). Bacteriol Rev. 1964 Dec;28:458–471. doi: 10.1128/br.28.4.458-471.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shimomura Y., Gangarosa L. P., Sr, Kataoka M., Hill J. M. HSV-1 shedding by lontophoresis of 6-hydroxydopamine followed by topical epinephrine. Invest Ophthalmol Vis Sci. 1983 Dec;24(12):1588–1594. [PubMed] [Google Scholar]
  26. 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]
  27. Stroop W. G., Rock D. L., Fraser N. W. Localization of herpes simplex virus in the trigeminal and olfactory systems of the mouse central nervous system during acute and latent infections by in situ hybridization. Lab Invest. 1984 Jul;51(1):27–38. [PubMed] [Google Scholar]
  28. Tenser R. B., Dawson M., Ressel S. J., Dunstan M. E. Detection of herpes simplex virus mRNA in latently infected trigeminal ganglion neurons by in situ hybridization. Ann Neurol. 1982 Mar;11(3):285–291. doi: 10.1002/ana.410110309. [DOI] [PubMed] [Google Scholar]
  29. Wechsler S. L., Fields B. N. Intracellular synthesis of measles virus-specified polypeptides. J Virol. 1978 Jan;25(1):285–297. doi: 10.1128/jvi.25.1.285-297.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES