Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Oct;86(19):7596–7600. doi: 10.1073/pnas.86.19.7596

Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.

D Y Ho 1, E S Mocarski 1
PMCID: PMC298113  PMID: 2552449

Abstract

During latent infection by herpes simplex virus (HSV), an abundant latency-associated transcript (LAT) that is antisense to a predominant viral alpha gene (ICP0) is found localized in the nucleus of sensory neurons. We disrupted both copies of the LAT gene in the HSV-1 genome by insertion of the Escherichia coli lacZ gene under LAT promoter control. The resulting recombinant virus, RH142, does not express any detectable LAT in either latently or productively infected cells, although beta-galactosidase expression is readily detectable in sensory neurons of latently infected mice. Expression was first detectable 3 days postinoculation and continued at approximately the same level for the entire experimental period (56 days). beta-Galactosidase expression was not detectable at any time during RH142 replication in Vero cells. Thus, the kinetics of expression and cell-type specificity of the LAT gene are distinct from other HSV-1 genes that are expressed during productive growth. When latently infected trigeminal ganglia were explanted, RH142 reactivated from latency with the kinetics and an efficiency indistinguishable from the parental wild-type virus. These studies argue against any possible antisense regulatory mechanism of LAT in the regulation of viral gene expression or any role of LAT-encoded protein during the establishment or maintenance of latency in the mouse.

Full text

PDF

Images in this article

7598Image
on p.7598
7598Image
on p.7598
7598Image
on p.7598
7598Image
on p.7598
7599Image
on p.7599
7599Image
on p.7599
7599Image
on p.7599
7599Image
on p.7599
7599Image
on p.7599

Selected References

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

  1. Geballe A. P., Leach F. S., Mocarski E. S. Regulation of cytomegalovirus late gene expression: gamma genes are controlled by posttranscriptional events. J Virol. 1986 Mar;57(3):864–874. doi: 10.1128/jvi.57.3.864-874.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gordon Y. J., Johnson B., Romanowski E., Araullo-Cruz T. RNA complementary to herpes simplex virus type 1 ICP0 gene demonstrated in neurons of human trigeminal ganglia. J Virol. 1988 May;62(5):1832–1835. doi: 10.1128/jvi.62.5.1832-1835.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ho D. Y., Mocarski E. S. Beta-galactosidase as a marker in the peripheral and neural tissues of the herpes simplex virus-infected mouse. Virology. 1988 Nov;167(1):279–283. doi: 10.1016/0042-6822(88)90079-7. [DOI] [PubMed] [Google Scholar]
  4. Javier R. T., Stevens J. G., Dissette V. B., Wagner E. K. A herpes simplex virus transcript abundant in latently infected neurons is dispensable for establishment of the latent state. Virology. 1988 Sep;166(1):254–257. doi: 10.1016/0042-6822(88)90169-9. [DOI] [PubMed] [Google Scholar]
  5. Leib D. A., Coen D. M., Bogard C. L., Hicks K. A., Yager D. R., Knipe D. M., Tyler K. L., Schaffer P. A. Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. J Virol. 1989 Feb;63(2):759–768. doi: 10.1128/jvi.63.2.759-768.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Manning W. C., Mocarski E. S. Insertional mutagenesis of the murine cytomegalovirus genome: one prominent alpha gene (ie2) is dispensable for growth. Virology. 1988 Dec;167(2):477–484. [PubMed] [Google Scholar]
  7. Rock D. L., Nesburn A. B., Ghiasi H., Ong J., Lewis T. L., Lokensgard J. R., Wechsler S. L. Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1. J Virol. 1987 Dec;61(12):3820–3826. doi: 10.1128/jvi.61.12.3820-3826.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Roizman B., Sears A. E. An inquiry into the mechanisms of herpes simplex virus latency. Annu Rev Microbiol. 1987;41:543–571. doi: 10.1146/annurev.mi.41.100187.002551. [DOI] [PubMed] [Google Scholar]
  9. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Spaete R. R., Mocarski E. S. Insertion and deletion mutagenesis of the human cytomegalovirus genome. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7213–7217. doi: 10.1073/pnas.84.20.7213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Spaete R. R., Mocarski E. S. Regulation of cytomegalovirus gene expression: alpha and beta promoters are trans activated by viral functions in permissive human fibroblasts. J Virol. 1985 Oct;56(1):135–143. doi: 10.1128/jvi.56.1.135-143.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Spivack J. G., Fraser N. W. Detection of herpes simplex virus type 1 transcripts during latent infection in mice. J Virol. 1987 Dec;61(12):3841–3847. doi: 10.1128/jvi.61.12.3841-3847.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Spivack J. G., Fraser N. W. Expression of herpes simplex virus type 1 latency-associated transcripts in the trigeminal ganglia of mice during acute infection and reactivation of latent infection. J Virol. 1988 May;62(5):1479–1485. doi: 10.1128/jvi.62.5.1479-1485.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Steiner I., Spivack J. G., Lirette R. P., Brown S. M., MacLean A. R., Subak-Sharpe J. H., Fraser N. W. Herpes simplex virus type 1 latency-associated transcripts are evidently not essential for latent infection. EMBO J. 1989 Feb;8(2):505–511. doi: 10.1002/j.1460-2075.1989.tb03404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Villarreal L. P., Berg P. Hybridization in situ of SV40 plaques: detection of recombinant SV40 virus carrying specific sequences of nonviral DNA. Science. 1977 Apr 8;196(4286):183–185. doi: 10.1126/science.191907. [DOI] [PubMed] [Google Scholar]
  17. Wagner E. K., Devi-Rao G., Feldman L. T., Dobson A. T., Zhang Y. F., Flanagan W. M., Stevens J. G. Physical characterization of the herpes simplex virus latency-associated transcript in neurons. J Virol. 1988 Apr;62(4):1194–1202. doi: 10.1128/jvi.62.4.1194-1202.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wagner E. K., Flanagan W. M., Devi-Rao G., Zhang Y. F., Hill J. M., Anderson K. P., Stevens J. G. The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection. J Virol. 1988 Dec;62(12):4577–4585. doi: 10.1128/jvi.62.12.4577-4585.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wechsler S. L., Nesburn A. B., Watson R., Slanina S. M., Ghiasi H. Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames. J Virol. 1988 Nov;62(11):4051–4058. doi: 10.1128/jvi.62.11.4051-4058.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wechsler S. L., Nesburn A. B., Zwaagstra J., Ghiasi H. Sequence of the latency-related gene of herpes simplex virus type 1. Virology. 1989 Jan;168(1):168–172. doi: 10.1016/0042-6822(89)90416-9. [DOI] [PubMed] [Google Scholar]
  21. Wildy P. Herpesvirus. Intervirology. 1986;25(3):117–140. doi: 10.1159/000149666. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES