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Journal of Virology, August 2008, p. 7443-7455, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00388-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Type 1 ICP27 Regulates Expression of a Variant, Secreted Form of Glycoprotein C by an Intron Retention Mechanism{triangledown}

Lenka Sedlackova,1 Keith D. Perkins,1 Joy Lengyel,1 Anna K. Strain,1 Vicky L. van Santen,2 and Stephen A. Rice1*

Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455,1 Department of Pathobiology, 264 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849-55192

Received 22 February 2008/ Accepted 12 May 2008

We previously showed that herpes simplex virus type 1 (HSV-1) immediate-early (IE) protein ICP27 can posttranscriptionally stimulate mRNA accumulation from a transfected viral late gene encoding glycoprotein C (gC) (K. D. Perkins, J. Gregonis, S. Borge, and S. A. Rice, J. Virol. 77:9872-9884, 2003). We began this study by asking whether ICP27 homologs from other herpesviruses can also mediate this activity. Although the homologs from varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) were inactive, the homolog from bovine herpesvirus 4 (BHV-4), termed HORF1/2, was a very efficient transactivator. Surprisingly, most of the mRNA produced via HORF1/2 transactivation was 225 nucleotides shorter than expected due to the removal of a previously undescribed intron from the gC transcript. We found that the gC mRNA produced in the absence of transactivation was also mostly spliced. In contrast, gC mRNA produced by ICP27 transactivation was predominantly unspliced. Based on these results, we conclude that ICP27 has two distinct effects on the transfected gC gene: it (i) stimulates mRNA accumulation and (ii) promotes the retention of an intron. Interestingly, the spliced transcript encodes a variant of gC that lacks its transmembrane domain and is secreted from transfected cells. As the gC splicing signals are conserved among several HSV-1 strains, we investigated whether the variant gC is expressed during viral infection. We report here that both the spliced transcript and its encoded protein are readily detected in Vero cells infected with three different laboratory strains of wild-type HSV-1. Moreover, the variant gC is efficiently secreted from infected cells. We have designated this alternate form of the protein as gCsec. As the extracellular domain of gC is known to bind heparan sulfate-containing proteoglycans and to inhibit the complement cascade via an interaction with complement component C3b, we speculate that gCsec could function as a secreted virulence factor.

* Corresponding author. Mailing address: Department of Microbiology, University of Minnesota Medical School, Mayo Mail Code 196, 420 Delaware St. S.E., Minneapolis, MN 55455. Phone: (612) 626-4183. Fax: (612) 626-0623. E-mail: ricex019{at}umn.edu

{triangledown} Published ahead of print on 21 May 2008.

Journal of Virology, August 2008, p. 7443-7455, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00388-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nojima, T., Oshiro-Ideue, T., Nakanoya, H., Kawamura, H., Morimoto, T., Kawaguchi, Y., Kataoka, N., Hagiwara, M. (2009). Herpesvirus protein ICP27 switches PML isoform by altering mRNA splicing. Nucleic Acids Res 37: 6515-6527 [Abstract] [Full Text]  


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