This Article Full Text Full Text (PDF) An author's correction has been published Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lei, P. Articles by Andreadis, S. T. Search for Related Content PubMed PubMed Citation Articles by Lei, P. Articles by Andreadis, S. T.

 Previous Article  |  Next Article 

Journal of Virology, September 2002, p. 8722-8728, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8722-8728.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Retrovirus-Associated Heparan Sulfate Mediates Immobilization and Gene Transfer on Recombinant Fibronectin

Pedro Lei, Bharat Bajaj, and Stelios T. Andreadis^*

Bioengineering Laboratory, Department of Chemical Engineering, University at Buffalo, State University of New York, Amherst, New York 14260

Received 21 November 2001/ Accepted 5 June 2002

Recombinant retroviruses have been shown to bind to fibronectin (FN) and increase the efficiency of gene transfer to a variety of cell types. Despite recent work to optimize gene transfer on recombinant FN, the mechanism of retrovirus binding to FN and the interactions of target cells with the bound virus remain elusive. We investigated the roles of virus surface glycoprotein (gp70), cell-conditioned medium, and proteoglycans in mediating retrovirus binding to FN. We also examined the role of Polybrene (PB) in these interactions. We found that gp70 is not involved in retrovirus binding to FN. Immobilization of the virus, however, does not overcome its receptor requirement, and gp70 is still needed for successful gene transfer. Our results clearly show that retrovirus binds FN through virus-associated heparan sulfate (HS) and that binding is necessary for transduction without PB. Two distinct modes of gene transfer occur depending on PB: (i) in the presence of PB, retrovirus interacts directly with the target cells; and (ii) in the absence of PB, retrovirus binds to FN and target cells interact with the immobilized virus. PB may promote the former mode by interacting with the virus HS and reducing the negative charge of the viral particles. Interestingly, the latter mode is more efficient, leading to significantly enhanced gene transfer. A better understanding of these interactions may provide insight into virus-cell interactions and lead to a more rational design of transduction protocols.

---

* Corresponding author. Mailing address: Bioengineering Laboratory, 908 Furnas Hall, Department of Chemical Engineering, State University of New York at Buffalo, Amherst, NY 14260. Phone: (716) 645-2911, ext. 2204. Fax: (716) 645-3822. E-mail: sandread{at}eng.buffalo.edu.

---

Journal of Virology, September 2002, p. 8722-8728, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8722-8728.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Beer, C., Pedersen, L. (2007). Matrix Fibronectin Binds Gammaretrovirus and Assists in Entry: New Light on Viral Infections. J. Virol. 81: 8247-8257 [Abstract] [Full Text]  
• Beer, C., Andersen, D. S., Rojek, A., Pedersen, L. (2005). Caveola-Dependent Endocytic Entry of Amphotropic Murine Leukemia Virus. J. Virol. 79: 10776-10787 [Abstract] [Full Text]  
• Kahl, C. A., Marsh, J., Fyffe, J., Sanders, D. A., Cornetta, K. (2004). Human Immunodeficiency Virus Type 1-Derived Lentivirus Vectors Pseudotyped with Envelope Glycoproteins Derived from Ross River Virus and Semliki Forest Virus. J. Virol. 78: 1421-1430 [Abstract] [Full Text]