Abstract
During latent infection of neurons with herpes simplex virus type 1, viral transcription is restricted to the latency-associated transcripts (LATs). These RNAs contain open reading frames, but detection of a protein encoded by the LATs has not been reported. We used immunocytochemical techniques to demonstrate that an antiserum directed against a bacterially expressed fusion protein containing part of a LAT-encoded polypeptide recognized an antigen present in primary neurons latently infected in vitro. This antigen (called LAA, for latency-associated antigen) was not detected in mock-infected neurons, in productively infected Vero cells, or in neurons latently infected with a mutant virus carrying a deletion in the LAT gene. By Western immunoblot analysis, we demonstrated the presence of a protein with an apparent molecular mass of 80 kDa recognized by the anti-LAA antiserum in latently infected neurons.
Full text
PDF![2724](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c5/240637/db90b2b0de56/jvirol00048-0582.png)
![2725](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c5/240637/f6ffe20ab531/jvirol00048-0583.png)
![2726](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c5/240637/4e041cafd68e/jvirol00048-0584.png)
![2727](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c5/240637/cd8cfd24965c/jvirol00048-0585.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Block T. M., Spivack J. G., Steiner I., Deshmane S., McIntosh M. T., Lirette R. P., Fraser N. W. A herpes simplex virus type 1 latency-associated transcript mutant reactivates with normal kinetics from latent infection. J Virol. 1990 Jul;64(7):3417–3426. doi: 10.1128/jvi.64.7.3417-3426.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clements G. B., Stow N. D. A herpes simplex virus type 1 mutant containing a deletion within immediate early gene 1 is latency-competent in mice. J Gen Virol. 1989 Sep;70(Pt 9):2501–2506. doi: 10.1099/0022-1317-70-9-2501. [DOI] [PubMed] [Google Scholar]
- Croen K. D., Ostrove J. M., Dragovic L. J., Smialek J. E., Straus S. E. Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene "anti-sense" transcript by in situ hybridization. N Engl J Med. 1987 Dec 3;317(23):1427–1432. doi: 10.1056/NEJM198712033172302. [DOI] [PubMed] [Google Scholar]
- Deatly A. M., Spivack J. G., Lavi E., O'Boyle D. R., 2nd, Fraser N. W. Latent herpes simplex virus type 1 transcripts in peripheral and central nervous system tissues of mice map to similar regions of the viral genome. J Virol. 1988 Mar;62(3):749–756. doi: 10.1128/jvi.62.3.749-756.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dobson A. T., Sederati F., Devi-Rao G., Flanagan W. M., Farrell M. J., Stevens J. G., Wagner E. K., Feldman L. T. Identification of the latency-associated transcript promoter by expression of rabbit beta-globin mRNA in mouse sensory nerve ganglia latently infected with a recombinant herpes simplex virus. J Virol. 1989 Sep;63(9):3844–3851. doi: 10.1128/jvi.63.9.3844-3851.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill J. M., Sedarati F., Javier R. T., Wagner E. K., Stevens J. G. Herpes simplex virus latent phase transcription facilitates in vivo reactivation. Virology. 1990 Jan;174(1):117–125. doi: 10.1016/0042-6822(90)90060-5. [DOI] [PubMed] [Google Scholar]
- Ho D. Y., Mocarski E. S. Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7596–7600. doi: 10.1073/pnas.86.19.7596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Leib D. A., Bogard C. L., Kosz-Vnenchak M., Hicks K. A., Coen D. M., Knipe D. M., Schaffer P. A. A deletion mutant of the latency-associated transcript of herpes simplex virus type 1 reactivates from the latent state with reduced frequency. J Virol. 1989 Jul;63(7):2893–2900. doi: 10.1128/jvi.63.7.2893-2900.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Price R. W. Neurobiology of human herpesvirus infections. CRC Crit Rev Clin Neurobiol. 1986;2(1):61–123. [PubMed] [Google Scholar]
- 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]
- Spindler K. R., Rosser D. S., Berk A. J. Analysis of adenovirus transforming proteins from early regions 1A and 1B with antisera to inducible fusion antigens produced in Escherichia coli. J Virol. 1984 Jan;49(1):132–141. doi: 10.1128/jvi.49.1.132-141.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Stevens J. G. Human herpesviruses: a consideration of the latent state. Microbiol Rev. 1989 Sep;53(3):318–332. doi: 10.1128/mr.53.3.318-332.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Stow N. D., Stow E. C. Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol. 1986 Dec;67(Pt 12):2571–2585. doi: 10.1099/0022-1317-67-12-2571. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Wilcox C. L., Johnson E. M., Jr Characterization of nerve growth factor-dependent herpes simplex virus latency in neurons in vitro. J Virol. 1988 Feb;62(2):393–399. doi: 10.1128/jvi.62.2.393-399.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Wilcox C. L., Smith R. L., Freed C. R., Johnson E. M., Jr Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro. J Neurosci. 1990 Apr;10(4):1268–1275. doi: 10.1523/JNEUROSCI.10-04-01268.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]