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 Struyf, F.
Right arrow Articles by Spear, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Struyf, F.
Right arrow Articles by Spear, P. G.

 Previous Article  |  Next Article 

Journal of Virology, December 2002, p. 12940-12950, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12940-12950.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mutations in the N-Terminal Domains of Nectin-1 and Nectin-2 Reveal Differences in Requirements for Entry of Various Alphaherpesviruses and for Nectin-Nectin Interactions

Frank Struyf,1,2 Wanda M. Martinez,1 and Patricia G. Spear1*

Department of Microbiology-Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611,1 Laboratory of Clinical and Epidemiological Virology, Department of Microbiology and Immunology, Rega Institute for Medical Research, 3000 Leuven, Belgium2

Received 4 June 2002/ Accepted 12 September 2002

Nectin-1 and nectin-2 are related molecules that can function with different specificities as entry receptors for mammalian alphaherpesviruses through interaction with viral glycoprotein D (gD). The normal function of members of the nectin family is to mediate cell-cell adhesion through homotypic and heterotypic nectin-nectin interactions in cadherin-based adherens junctions. We examined mutations in three equivalent regions of the N-terminal V-like domains of nectin-1 and nectin-2 to test the effects on entry of various alphaherpesviruses, nectin-nectin interactions, and interactions of the mutant nectins with gD. Mutations in region I previously shown to severely impair herpes simplex virus (HSV) entry activity, but not pseudorabies virus (PRV) or bovine herpesvirus 1 (BHV-1) entry, did not reduce homotypic trans interactions for either nectin-1 or nectin-2 or binding of nectin-3 to nectin-1. Mutations in region II, patterned after a reported single-nucleotide polymorphism in nectin-2, enhanced intracellular accumulation of both nectin-1 and nectin-2 and had a deleterious effect on all of the activities under study. Mutations in region III previously shown to reduce homotypic trans interactions of nectin-2 impaired the entry of PRV and BHV-1 when introduced into either nectin-1 or nectin-2, but only the nectin-2 mutation reduced HSV entry activity. Binding of nectin-1 to nectin-3 was not affected. Effects of the nectin-1 and nectin-2 mutations on interactions with gD did not necessarily correlate with entry activity of the mutant receptors. We can conclude that structural requirements for HSV entry, PRV and BHV-1 entry, and homotypic and heterotypic trans interactions are all different despite the previously reported ability of HSV and HSV gD to inhibit trans interactions.

* Corresponding author. Mailing address: Northwestern University, The Feinberg School of Medicine, Department of Microbiology-Immunology, Room Searle 6-447, Mail Code S213, 320 E. Superior St., Chicago, IL 60611. Phone: (312) 503-8230. Fax: (312) 503-1339. E-mail: p-spear{at}northwestern.edu.

Journal of Virology, December 2002, p. 12940-12950, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12940-12950.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Struyf, F., Plate, A. E., Spear, P. G. (2005). Deletion of the Second Immunoglobulin-Like Domain of Nectin-1 Alters Its Intracellular Processing and Localization and Ability To Mediate Entry of Herpes Simplex Virus. J. Virol. 79: 3841-3845 [Abstract] [Full Text]  
  • Yoon, M., Spear, P. G. (2004). Random mutagenesis of the gene encoding a viral ligand for multiple cell entry receptors to obtain viral mutants altered for receptor usage. Proc. Natl. Acad. Sci. USA 101: 17252-17257 [Abstract] [Full Text]  
  • Manoj, S., Jogger, C. R., Myscofski, D., Yoon, M., Spear, P. G. (2004). Inaugural Article: Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism. Proc. Natl. Acad. Sci. USA 101: 12414-12421 [Abstract] [Full Text]  
  • Spear, P. G., Longnecker, R. (2003). Herpesvirus Entry: an Update. J. Virol. 77: 10179-10185 [Full Text]  
  • Yoon, M., Zago, A., Shukla, D., Spear, P. G. (2003). Mutations in the N Termini of Herpes Simplex Virus Type 1 and 2 gDs Alter Functional Interactions with the Entry/Fusion Receptors HVEM, Nectin-2, and 3-O-Sulfated Heparan Sulfate but Not with Nectin-1. J. Virol. 77: 9221-9231 [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]  


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