Abstract
The herpes simplex virus type 1 virion host shutoff protein has four domains whose sequences are conserved only among neurotropic herpesviruses. Mutant viruses with 29- and 31-amino-acid deletions in domains III and IV but outside of the domain required for interaction with VP16 were generated. The mutants failed to induce cellular RNA degradation and showed impaired virulence in mice. Domains III and IV are therefore required for both shutoff and virulence.
Full Text
The Full Text of this article is available as a PDF (273.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Berthomme H., Jacquemont B., Epstein A. The pseudorabies virus host-shutoff homolog gene: nucleotide sequence and comparison with alphaherpesvirus protein counterparts. Virology. 1993 Apr;193(2):1028–1032. doi: 10.1006/viro.1993.1221. [DOI] [PubMed] [Google Scholar]
- 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]
- Fenwick M. L., Everett R. D. Inactivation of the shutoff gene (UL41) of herpes simplex virus types 1 and 2. J Gen Virol. 1990 Dec;71(Pt 12):2961–2967. doi: 10.1099/0022-1317-71-12-2961. [DOI] [PubMed] [Google Scholar]
- Fenwick M. L., McMenamin M. M. Early virion-associated suppression of cellular protein synthesis by herpes simplex virus is accompanied by inactivation of mRNA. J Gen Virol. 1984 Jul;65(Pt 7):1225–1228. doi: 10.1099/0022-1317-65-7-1225. [DOI] [PubMed] [Google Scholar]
- Fenwick M. L., Walker M. J. Suppression of the synthesis of cellular macromolecules by herpes simplex virus. J Gen Virol. 1978 Oct;41(1):37–51. doi: 10.1099/0022-1317-41-1-37. [DOI] [PubMed] [Google Scholar]
- Fenwick M., Morse L. S., Roizman B. Anatomy of herpes simplex virus DNA. XI. Apparent clustering of functions effecting rapid inhibition of host DNA and protein synthesis. J Virol. 1979 Feb;29(2):825–827. doi: 10.1128/jvi.29.2.825-827.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones F. E., Smibert C. A., Smiley J. R. Mutational analysis of the herpes simplex virus virion host shutoff protein: evidence that vhs functions in the absence of other viral proteins. J Virol. 1995 Aug;69(8):4863–4871. doi: 10.1128/jvi.69.8.4863-4871.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz J. P., Bodin E. T., Coen D. M. Quantitative polymerase chain reaction analysis of herpes simplex virus DNA in ganglia of mice infected with replication-incompetent mutants. J Virol. 1990 Sep;64(9):4288–4295. doi: 10.1128/jvi.64.9.4288-4295.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwong A. D., Frenkel N. Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1926–1930. doi: 10.1073/pnas.84.7.1926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwong A. D., Kruper J. A., Frenkel N. Herpes simplex virus virion host shutoff function. J Virol. 1988 Mar;62(3):912–921. doi: 10.1128/jvi.62.3.912-921.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
- Nishioka Y., Silverstein S. Alterations in the protein synthetic apparatus of Friend erythroleukemia cells infected with vesicular stomatitis virus or herpes simplex virus. J Virol. 1978 Jan;25(1):422–426. doi: 10.1128/jvi.25.1.422-426.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishioka Y., Silverstein S. Degradation of cellular mRNA during infection by herpes simplex virus. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2370–2374. doi: 10.1073/pnas.74.6.2370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pak A. S., Everly D. N., Knight K., Read G. S. The virion host shutoff protein of herpes simplex virus inhibits reporter gene expression in the absence of other viral gene products. Virology. 1995 Aug 20;211(2):491–506. doi: 10.1006/viro.1995.1431. [DOI] [PubMed] [Google Scholar]
- Read G. S., Frenkel N. Herpes simplex virus mutants defective in the virion-associated shutoff of host polypeptide synthesis and exhibiting abnormal synthesis of alpha (immediate early) viral polypeptides. J Virol. 1983 May;46(2):498–512. doi: 10.1128/jvi.46.2.498-512.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Read G. S., Karr B. M., Knight K. Isolation of a herpes simplex virus type 1 mutant with a deletion in the virion host shutoff gene and identification of multiple forms of the vhs (UL41) polypeptide. J Virol. 1993 Dec;67(12):7149–7160. doi: 10.1128/jvi.67.12.7149-7160.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmelter J., Knez J., Smiley J. R., Capone J. P. Identification and characterization of a small modular domain in the herpes simplex virus host shutoff protein sufficient for interaction with VP16. J Virol. 1996 Apr;70(4):2124–2131. doi: 10.1128/jvi.70.4.2124-2131.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smibert C. A., Johnson D. C., Smiley J. R. Identification and characterization of the virion-induced host shutoff product of herpes simplex virus gene UL41. J Gen Virol. 1992 Feb;73(Pt 2):467–470. doi: 10.1099/0022-1317-73-2-467. [DOI] [PubMed] [Google Scholar]
- Smibert C. A., Popova B., Xiao P., Capone J. P., Smiley J. R. Herpes simplex virus VP16 forms a complex with the virion host shutoff protein vhs. J Virol. 1994 Apr;68(4):2339–2346. doi: 10.1128/jvi.68.4.2339-2346.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smibert C. A., Smiley J. R. Differential regulation of endogenous and transduced beta-globin genes during infection of erythroid cells with a herpes simplex virus type 1 recombinant. J Virol. 1990 Aug;64(8):3882–3894. doi: 10.1128/jvi.64.8.3882-3894.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steiner I., Spivack J. G., Deshmane S. L., Ace C. I., Preston C. M., Fraser N. W. A herpes simplex virus type 1 mutant containing a nontransinducing Vmw65 protein establishes latent infection in vivo in the absence of viral replication and reactivates efficiently from explanted trigeminal ganglia. J Virol. 1990 Apr;64(4):1630–1638. doi: 10.1128/jvi.64.4.1630-1638.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strelow L. I., Leib D. A. Role of the virion host shutoff (vhs) of herpes simplex virus type 1 in latency and pathogenesis. J Virol. 1995 Nov;69(11):6779–6786. doi: 10.1128/jvi.69.11.6779-6786.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strom T., Frenkel N. Effects of herpes simplex virus on mRNA stability. J Virol. 1987 Jul;61(7):2198–2207. doi: 10.1128/jvi.61.7.2198-2207.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zelus B. D., Stewart R. S., Ross J. The virion host shutoff protein of herpes simplex virus type 1: messenger ribonucleolytic activity in vitro. J Virol. 1996 Apr;70(4):2411–2419. doi: 10.1128/jvi.70.4.2411-2419.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]