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Journal of Virology, May 2005, p. 5272-5277, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5272-5277.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of a Recombinant Herpes Simplex Virus 1 Designed To Enter Cells via the IL13R{alpha}2 Receptor of Malignant Glioma Cells

Guoying Zhou and Bernard Roizman*

The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, Illinois 60637

Received 3 November 2004/ Accepted 21 December 2004

Malignant glioma tumor cells in situ exhibit on their surfaces the interleukin 13 (IL-13) receptor designated IL13R{alpha}2. To target herpes simplex virus 1 to this receptor, we constructed a recombinant virus (R5111) in which the known heparan sulfate binding sites in glycoproteins B and C were deleted and IL-13 was inserted into both glycoproteins C and D. We also transduced a baby hamster kidney cell line lacking the known viral receptors (J1-1) and Vero cells with a plasmid encoding IL13R{alpha}2. The J1-1 derivative (J-13R) cell line is susceptible to and replicates the R5111 recombinant virus but not the wild-type parent virus. We report the following. (i) Expression of IL13R{alpha}2 was rapidly lost from the surface of transduced cells grown in culture. The loss appeared to be related to ligands present in fetal bovine serum in the medium. None of the malignant glioma cell lines cultivated in vitro and tested to date exhibited the IL13R{alpha}2 receptor. (ii) Soluble IL-13 but not IL-4 or IL-2 blocked the replication of R5111 recombinant virus in J-13R cells. (iii) The endocytosis inhibitor PD98059 blocked the replication in J1-1 cells of a mutant lacking glycoprotein D (gD–/–) but not the replication of R5111 in the J-13R cells. We conclude that R5111 enters cells via its interaction with the IL13R{alpha}2 receptor in a manner that cannot be differentiated from the interaction of wild-type virus with its receptors.

* Corresponding author. Mailing address: The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, Il 60637. Phone: (773) 702-1898. Fax: (773) 702-1631. E-mail: bernard.roizman{at}bsd.uchicago.edu.

Journal of Virology, May 2005, p. 5272-5277, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5272-5277.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Menotti, L., Cerretani, A., Hengel, H., Campadelli-Fiume, G. (2008). Construction of a Fully Retargeted Herpes Simplex Virus 1 Recombinant Capable of Entering Cells Solely via Human Epidermal Growth Factor Receptor 2. J. Virol. 82: 10153-10161 [Abstract] [Full Text]  
  • Zhou, G., Roizman, B. (2007). Separation of receptor-binding and profusogenic domains of glycoprotein D of herpes simplex virus 1 into distinct interacting proteins. Proc. Natl. Acad. Sci. USA 104: 4142-4146 [Abstract] [Full Text]  
  • Menotti, L., Cerretani, A., Campadelli-Fiume, G. (2006). A Herpes Simplex Virus Recombinant That Exhibits a Single-Chain Antibody to HER2/neu Enters Cells through the Mammary Tumor Receptor, Independently of the gD Receptors.. J. Virol. 80: 5531-5539 [Abstract] [Full Text]  
  • Zhou, G., Roizman, B. (2006). Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13{alpha}2 receptor. Proc. Natl. Acad. Sci. USA 103: 5508-5513 [Abstract] [Full Text]  


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