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 Martinez, W. M.
Right arrow Articles by Spear, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martinez, W. M.
Right arrow Articles by Spear, P. G.

 Previous Article  |  Next Article 

Journal of Virology, November 2001, p. 11185-11195, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11185-11195.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Structural Features of Nectin-2 (HveB) Required for Herpes Simplex Virus Entry

Wanda M. Martinez and Patricia G. Spear*

Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611

Received 14 June 2001/Accepted 8 August 2001

One step in the process of herpes simplex virus (HSV) entry into cells is the binding of viral glycoprotein D (gD) to a cellular receptor. Human nectin-2 (also known as HveB and Prr2), a member of the immunoglobulin (Ig) superfamily, serves as a gD receptor for the entry of HSV-2, variant forms of HSV-1 that have amino acid substitutions at position 25 or 27 of gD (for example, HSV-1/Rid), and porcine pseudorabies virus (PRV). The gD binding region of nectin-2 is believed to be localized to the N-terminal variable-like (V) Ig domain. In order to identify specific amino acid sequences in nectin-2 that are important for HSV entry activity, chimeric molecules were constructed by exchange of sequences between human nectin-2 and its mouse homolog, mouse nectin-2, which mediates entry of PRV but not HSV-1 or HSV-2. The nectin-2 chimeric molecules were expressed in Chinese hamster ovary cells, which normally lack a gD receptor, and tested for cell surface expression and viral entry activity. As expected, chimeric molecules containing the V domain of human nectin-2 exhibited HSV entry activity. Replacement of either of two small regions in the V domain of mouse nectin-2 with amino acids from the equivalent positions in human nectin-2 (amino acids 75 to 81 or 89) transferred HSV-1/Rid entry activity to mouse nectin-2. The resulting chimeras also exhibited enhanced HSV-2 entry activity and gained the ability to mediate wild-type HSV-1 entry. Replacement of amino acid 89 of human nectin-2 with the corresponding mouse amino acid (M89F) eliminated HSV entry activity. These results identify two different amino acid sequences, predicted to lie adjacent to the C' and C" beta-strands of the V domain, that are critical for HSV entry activity. This region is homologous to the human immunodeficiency virus binding region of CD4 and to the poliovirus binding region of CD155.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University Medical School, 320 E. Superior St., Mailcode S213, Chicago, IL 60611. Phone: (312) 503-8230. Fax: (312) 503-1339. E-mail: p-spear{at}northwestern.edu.

Journal of Virology, November 2001, p. 11185-11195, Vol. 75, No. 22
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.22.11185-11195.2001
Copyright © 2001, 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]  
  • Linehan, M. M., Richman, S., Krummenacher, C., Eisenberg, R. J., Cohen, G. H., Iwasaki, A. (2004). In Vivo Role of Nectin-1 in Entry of Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 through the Vaginal Mucosa. J. Virol. 78: 2530-2536 [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]  
  • Zago, A., Spear, P. G. (2003). Differences in the N Termini of Herpes Simplex Virus Type 1 and 2 gDs That Influence Functional Interactions with the Human Entry Receptor Nectin-2 and an Entry Receptor Expressed in Chinese Hamster Ovary Cells. J. Virol. 77: 9695-9699 [Abstract] [Full Text]  
  • Koelle, D. M., Corey, L. (2003). Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research. Clin. Microbiol. Rev. 16: 96-113 [Abstract] [Full Text]  
  • Struyf, F., Martinez, W. M., Spear, P. G. (2002). 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. J. Virol. 76: 12940-12950 [Abstract] [Full Text]  
  • Martinez, W. M., Spear, P. G. (2002). Amino Acid Substitutions in the V Domain of Nectin-1 (HveC) That Impair Entry Activity for Herpes Simplex Virus Types 1 and 2 but Not for Pseudorabies Virus or Bovine Herpesvirus 1. J. Virol. 76: 7255-7262 [Abstract] [Full Text]  
  • Menotti, L., Casadio, R., Bertucci, C., Lopez, M., Campadelli-Fiume, G. (2002). 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. J. Virol. 76: 5463-5471 [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»