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Journal of Virology, December 2007, p. 13424-13434, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01528-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Type 2 Glycoprotein G Is Targeted by the Sulfated Oligo- and Polysaccharide Inhibitors of Virus Attachment to Cells{triangledown}

Beata Adamiak,1,3 Maria Ekblad,1 Tomas Bergström,1 Vito Ferro,2 and Edward Trybala1*

Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden,1 Drug Design Group, Progen Industries Ltd., 2806 Ipswich Rd., Darra QLD 4076, Australia,2 Department of Molecular Virology, University of Gdansk, Kladki 24, 80-822 Gdansk, Poland3

Received 12 July 2007/ Accepted 28 September 2007

Variants of herpes simplex virus type 2 (HSV-2) generated by virus passage in GMK-AH1 cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to PI-88 in their initial infection of cells and/or their cell-to-cell spread. The major alteration detected in all variants resistant to PI-88 in the initial infection of cells was a frameshift mutation(s) in the glycoprotein G (gG) gene that resulted in the lack of protein expression. Molecular transfer of the altered gG gene into the wild-type background confirmed that the gG-deficient recombinants were resistant to PI-88. In addition to PI-88, all gG-deficient variants of HSV-2 were resistant to the sulfated polysaccharide heparin. The gG-deficient virions were capable of attaching to cells, and this activity was relatively resistant to PI-88. In addition to having a drug-resistant phenotype, the gG-deficient variants were inefficiently released from infected cells. Purified gG bound to heparin and showed the cell-binding activity which was inhibited by PI-88. Many PI-88 variants produced syncytia in cultured cells and contained alterations in gB, including the syncytium-inducing L792P amino acid substitution. Although this phenotype can enhance the lateral spread of HSV in cells, it conferred no virus resistance to PI-88. Some PI-88 variants also contained occasional alterations in gC, gD, gE, gK, and UL24. In conclusion, we found that glycoprotein gG, a mucin-like component of the HSV-2 envelope, was targeted by sulfated oligo- and polysaccharides. This is a novel finding that suggests the involvement of HSV-2 gG in interactions with sulfated polysaccharides, including cell surface glycosaminoglycans.

* Corresponding author. Mailing address: Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden. Phone: 46-31-3424744. Fax: 46-31-827032. E-mail: edward.trybala{at}microbio.gu.se

{triangledown} Published ahead of print on 10 September 2007.

Journal of Virology, December 2007, p. 13424-13434, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01528-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Van de Walle, G. R., Jarosinski, K. W., Osterrieder, N. (2008). Alphaherpesviruses and Chemokines: Pas de Deux Not Yet Brought to Perfection. J. Virol. 82: 6090-6097 [Full Text]  


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