Abstract
ABSTRACT During lytic infections, the virion host shutoff (Vhs) protein (UL41) of herpes simplex virus destabilizes both host and viral mRNAs. By accelerating mRNA decay, it helps determine the levels and kinetics of viral and cellular gene expression. In vivo, Vhs shows a strong preference for mRNAs, as opposed to non-mRNAs, and degrades the 5′ end of mRNAs prior to the 3′ end. In contrast, partially purified Vhs is not restricted to mRNAs and causes cleavage of target RNAs at various sites throughout the molecule. To explain this discrepancy, we searched for cellular proteins that interact with Vhs using the Saccharomyces cerevisiae two-hybrid system. Vhs was found to interact with the human translation initiation factor, eIF4H. This interaction was verified by glutathione S -transferase pull-down experiments and by coimmunoprecipitation of Vhs and epitope-tagged eIF4H from extracts of mammalian cells. The interaction was abolished by several point mutations in Vhs that abrogate its ability to degrade mRNAs in vivo. The results suggest that Vhs is a viral mRNA degradation factor that is targeted to mRNAs, and to regions of translation initiation, through an interaction with eIF4H.
References
44
Referenced
95
10.1017/S1355838298980451
10.1073/pnas.220425497
10.1093/nar/29.5.1156
10.1006/viro.1996.0341
10.1093/nar/24.13.2488
10.1074/jbc.270.11.6108
10.1128/JVI.73.9.7153-7164.1999
10.1128/JVI.73.11.9222-9231.1999
10.1128/jvi.71.10.7157-7166.1997
10.1128/JVI.73.11.9117-9129.1999
10.1099/0022-1317-65-7-1225
10.1038/340245a0
10.1146/annurev.biochem.68.1.913
10.1016/S0092-8674(00)00102-1
- Hershey J. W. B. Merrick W. C. Pathway and mechanism of initiation of protein synthesis Translational control of gene expression. Sonenberg N. Hershey J. W. B. Mathews M. B. 2000 33 89 Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y
- Jackson R. J. Translation initiation on picornavirus RNA Translational control of gene expression. Sonenberg N. Hershey J. W. B. Mathews M. B. 2000 869 900 Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y
10.1006/viro.1999.9986
10.1128/jvi.65.1.112-122.1991
10.1073/pnas.84.7.1926
10.1128/jvi.62.3.912-921.1988
10.1128/jvi.69.7.3987-3994.1995
10.1128/JVI.75.3.1172-1185.2001
10.1128/JVI.75.2.1072-1076.2001
10.1007/s003350010166
10.1016/S0959-437X(00)00063-0
10.1038/348091a0
10.1128/jvi.61.2.604-606.1987
10.1128/jvi.63.5.1897-1906.1989
10.1006/viro.1995.1431
10.1093/nar/26.9.2252
- Read G. S. Control of mRNA stability during herpes simplex virus infections mRNA metabolism and post-transcriptional gene regulation. Harford J. B. Morris D. R. 1997 311 321 Wiley-Liss Inc. New York N.Y
10.1128/jvi.46.2.498-512.1983
10.1128/jvi.67.12.7149-7160.1993
10.1074/jbc.274.50.35415
10.1074/jbc.273.13.7579
10.1074/jbc.274.18.12236
10.1128/mr.59.3.423-450.1995
10.1128/jvi.55.3.601-610.1985
- Schwartz D. C. Parker R. Interaction of mRNA translation and mRNA degradation in Saccharomyces cerevisiae Translational control of gene expression. Sonenberg N. Hershey J. W. B. Mathews M. B. 2000 807 826 Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y
10.1099/0022-1317-73-2-467
10.1093/nar/19.16.4459
10.1128/jvi.61.7.2198-2207.1987
10.1146/annurev.biochem.69.1.571
10.1128/jvi.70.4.2411-2419.1996
Dates
Type | When |
---|---|
Created | 23 years ago (July 27, 2002, 6:06 a.m.) |
Deposited | 3 years, 5 months ago (March 5, 2022, 1:24 a.m.) |
Indexed | 4 months ago (April 15, 2025, 9:32 a.m.) |
Issued | 23 years, 9 months ago (Nov. 1, 2001) |
Published | 23 years, 9 months ago (Nov. 1, 2001) |
Published Print | 23 years, 9 months ago (Nov. 1, 2001) |
@article{Feng_2001, title={mRNA Decay during Herpesvirus Infections: Interaction between a Putative Viral Nuclease and a Cellular Translation Factor}, volume={75}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.75.21.10272-10280.2001}, DOI={10.1128/jvi.75.21.10272-10280.2001}, number={21}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Feng, Pinghui and Everly, David N. and Read, G. Sullivan}, year={2001}, month=nov, pages={10272–10280} }