This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Menotti, L.
Right arrow Articles by Campadelli-Fiume, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Menotti, L.
Right arrow Articles by Campadelli-Fiume, G.

 Previous Article  |  Next Article 

Journal of Virology, June 2002, p. 5463-5471, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5463-5471.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Substitution in the Murine Nectin1 Receptor of a Single Conserved Amino Acid at a Position Distal from the Herpes Simplex Virus gD Binding Site Confers High-Affinity Binding to gD{dagger}

Laura Menotti,1 Rita Casadio,2 Carlo Bertucci,3 Marc Lopez,4 and Gabriella Campadelli-Fiume1*

Department of Experimental Pathology, Section on Microbiology and Virology,1 CIRB Laboratory of Biocomputing, Department of Biology,2 Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy,3 Institute of Cancer Biology and Immunology, Institut de la Santé et de la Recherche Médicale, Marseille, France4

Received 11 February 2002/ Accepted 4 March 2002

By analogy with its human nectin1 counterpart, murine nectin1 serves as a cellular receptor for the entry of herpes simplex virus (HSV) into murine cells. HSV entry mediated by either receptor is dependent on the viral glycoprotein D (gD). Whereas human nectin1 binds gD at high affinity and in a saturable manner, murine nectin1 binds gD in a barely detectable fashion, depending on the sensitivity of the assay. The immunoglobulin type V domain of murine nectin differs from its human counterpart in 11 amino acids. To identify the key residues responsible for the high-affinity binding of gD to human nectin1, we replaced each of the 11 divergent amino acids with the human counterparts singly or in groups in an incremental manner. Replacement in murine nectin1 of six amino acids that lie within the gD binding region of human nectin1 (previously mapped to residues 64 to 94, likely the CC'C'' surface) increased the gD binding activity to a limited extent. In contrast, the single P138L substitution, which lies distal from the gD binding site, markedly increased gD binding. This substitution, when coupled with downstream substitutions, exerted the greatest effect. Three-dimensional modeling of the nectin1 V domain suggested that P138 in murine nectin1 might decrease the stability of the V domain by reducing the size of ß-strand G. The results support the notion that the overall structure of V nectin1 plays a pivotal role in its ability to bind HSV gD.

* Corresponding author. Mailing address: Department of Experimental Pathology, Section on Microbiology and Virology, University of Bologna, Via San Giacomo 12, 40126 Bologna, Italy. Phone: 39 051 2094733. Fax: 39 051 2094735. E-mail: campadel{at}kaiser.alma.unibo.it.

{dagger} We dedicate this article to our late friend and colleague, Franco Tatò, University of Rome, for his contributions to virology and particularly for his efforts to have virology included as a discipline in the biological sciences.

Journal of Virology, June 2002, p. 5463-5471, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5463-5471.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gianni, T., Fato, R., Bergamini, C., Lenaz, G., Campadelli-Fiume, G. (2006). Hydrophobic {alpha}-Helices 1 and 2 of Herpes Simplex Virus gH Interact with Lipids, and Their Mimetic Peptides Enhance Virus Infection and Fusion.. J. Virol. 80: 8190-8198 [Abstract] [Full Text]  
  • Gianni, T., Piccoli, A., Bertucci, C., Campadelli-Fiume, G. (2006). Heptad Repeat 2 in Herpes Simplex Virus 1 gH Interacts with Heptad Repeat 1 and Is Critical for Virus Entry and Fusion. J. Virol. 80: 2216-2224 [Abstract] [Full Text]  
  • Fusco, D., Forghieri, C., Campadelli-Fiume, G. (2005). The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors. Proc. Natl. Acad. Sci. USA 102: 9323-9328 [Abstract] [Full Text]  
  • Gianni, T., Menotti, L., Campadelli-Fiume, G. (2005). A Heptad Repeat in Herpes Simplex Virus 1 gH, Located Downstream of the {alpha}-Helix with Attributes of a Fusion Peptide, Is Critical for Virus Entry and Fusion. J. Virol. 79: 7042-7049 [Abstract] [Full Text]  
  • Gianni, T., Campadelli-Fiume, G., Menotti, L. (2004). Entry of Herpes Simplex Virus Mediated by Chimeric Forms of Nectin1 Retargeted to Endosomes or to Lipid Rafts Occurs through Acidic Endosomes. J. Virol. 78: 12268-12276 [Abstract] [Full Text]  
  • Cocchi, F., Fusco, D., Menotti, L., Gianni, T., Eisenberg, R. J., Cohen, G. H., Campadelli-Fiume, G. (2004). The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry. Proc. Natl. Acad. Sci. USA 101: 7445-7450 [Abstract] [Full Text]  
  • Cocchi, F., Menotti, L., Di Ninni, V., Lopez, M., Campadelli-Fiume, G. (2004). The Herpes Simplex Virus JMP Mutant Enters Receptor-Negative J Cells through a Novel Pathway Independent of the Known Receptors nectin1, HveA, and nectin2. J. Virol. 78: 4720-4729 [Abstract] [Full Text]  
  • Krummenacher, C., Baribaud, I., Eisenberg, R. J., Cohen, G. H. (2003). Cellular Localization of Nectin-1 and Glycoprotein D during Herpes Simplex Virus Infection. J. Virol. 77: 8985-8999 [Abstract] [Full Text]  
  • Zhou, G., Avitabile, E., Campadelli-Fiume, G., Roizman, B. (2003). The Domains of Glycoprotein D Required To Block Apoptosis Induced by Herpes Simplex Virus 1 Are Largely Distinct from Those Involved in Cell-Cell Fusion and Binding to Nectin1. J. Virol. 77: 3759-3767 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»