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Journal of Virology, December 2004, p. 13562-13572, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13562-13572.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role of the VP16-Binding Domain of vhs in Viral Growth, Host Shutoff Activity, and Pathogenesis

Stephanie S. Strand1 and David A. Leib1,2*

Departments of Ophthalmology and Visual Sciences,1 Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri2

Received 6 April 2004/ Accepted 3 August 2004

The virion host shutoff (vhs) protein of herpes simplex virus type 1 causes the degradation of host and viral mRNA immediately upon infection of permissive cells. vhs can interact with VP16 through a 20-amino-acid binding domain, and viruses containing a deletion of this VP16-binding domain of vhs ({Delta}20) and a corresponding marker rescue ({Delta}20R) were constructed and characterized. Transient-transfection assays showed that this domain was dispensable for vhs activity. The {Delta}20 recombinant virus, however, was unable to induce mRNA degradation in the presence of actinomycin D, while degradation induced by {Delta}20R was equivalent to that for wild-type virus. {Delta}20, {Delta}20R, and KOS caused comparable RNA degradation in the absence of actinomycin D. Western blot analysis of infected cells indicated that comparable levels of vhs were expressed by {Delta}20, {Delta}20R, and KOS, and there was only a modest reduction of vhs packaging in {Delta}20. Immunoprecipitation of protein from cells infected with {Delta}20 and {Delta}20R showed equivalent coprecipitation of vhs and VP16. Pathogenesis studies with {Delta}20 showed a significant decrease in replication in the corneas, trigeminal ganglia, and brains, as well as a significant reduction in clinical disease and lethality, but no significant difference in the establishment of, or reactivation from, latency compared to results with KOS and {Delta}20R. These results suggest that the previously described VP16-binding domain is not required for vhs packaging or for binding to VP16. It is required, however, for RNA degradation activity of tegument-derived vhs and wild-type replication and virulence in mice.

* Corresponding author. Mailing address: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Box 8096, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-2689. Fax: (314) 362-3638. E-mail: leib{at}vision.wustl.edu.

Journal of Virology, December 2004, p. 13562-13572, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.13562-13572.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Sarma, N., Agarwal, D., Shiflett, L. A., Read, G. S. (2008). Small Interfering RNAs That Deplete the Cellular Translation Factor eIF4H Impede mRNA Degradation by the Virion Host Shutoff Protein of Herpes Simplex Virus. J. Virol. 82: 6600-6609 [Abstract] [Full Text]  
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