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 Bender, F. C.
Right arrow Articles by Eisenberg, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bender, F. C.
Right arrow Articles by Eisenberg, R. J.
Right arrowPubmed/NCBI databases
*Gene
*Substance via MeSH
Hazardous Substances DB
*HEPARIN

 Previous Article  |  Next Article 

Journal of Virology, September 2005, p. 11588-11597, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11588-11597.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Glycoprotein B Binds to Cell Surfaces Independently of Heparan Sulfate and Blocks Virus Entry

Florent C. Bender,1* J. Charles Whitbeck,1 Huan Lou,1 Gary H. Cohen,1 and Roselyn J. Eisenberg2

Department of Microbiology, School of Dental Medicine,1 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 191042

Received 3 May 2005/ Accepted 17 June 2005

Virion glycoproteins gB, gD, and gH/gL play essential roles for herpes simplex virus (HSV) entry. The function of gD is to interact with a cognate receptor, and soluble forms of gD block HSV entry by tying up cell surface receptors. Both gB and the nonessential gC interact with cell surface heparan sulfate proteoglycan (HSPG), promoting viral attachment. However, cells deficient in proteoglycan synthesis can still be infected by HSV. This suggests another function for gB. We found that a soluble truncated form of gB bound saturably to the surface of Vero, A431, HeLa, and BSC-1 cells, L-cells, and a mouse melanoma cell line expressing the gD receptor nectin-1. The HSPG analog heparin completely blocked attachment of the gC ectodomain to Vero cells. In contrast, heparin only partially blocked attachment of soluble gB, leaving 20% of the input gB still bound even at high concentrations of inhibitor. Moreover, heparin treatment removed soluble gC but not gB from the cell surface. These data suggest that a portion of gB binds to cells independently of HSPG. In addition, gB bound to two HSPG-deficient cell lines derived from L-cells. Gro2C cells are deficient in HSPG, and Sog9 cells are deficient in HSPG, as well as chondroitin sulfate proteoglycan (CSPG). To identify particular gB epitopes responsible for HSPG-independent binding, we used a panel of monoclonal antibodies (MAbs) to gB to block gB binding. Only those gB MAbs that neutralized virus blocked binding of soluble gB to the cells. HSV entry into Gro2C and Sog9 cells was reduced but still detectable relative to the parental L-cells, as previously reported. Importantly, entry into Gro2C cells was blocked by purified forms of either the gD or gB ectodomain. On a molar basis, the extent of inhibition by gB was similar to that seen with gD. Together, these results suggest that soluble gB binds specifically to the surface of different cell types independently of HSPG and CSPG and that by doing so, the protein inhibits entry. The results provide evidence for the existence of a cellular entry receptor for gB.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania, School of Dental Medicine, 240 S. 40th St., Levy Building, Room 217, Philadelphia, PA 19104. Phone: (215) 898-6558. Fax: (215) 898-8385. E-mail: fbender{at}biochem.dental.upenn.edu.

Journal of Virology, September 2005, p. 11588-11597, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11588-11597.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wright, C. C., Wisner, T. W., Hannah, B. P., Eisenberg, R. J., Cohen, G. H., Johnson, D. C. (2009). Fusion between Perinuclear Virions and the Outer Nuclear Membrane Requires the Fusogenic Activity of Herpes Simplex Virus gB. J. Virol. 83: 11847-11856 [Abstract] [Full Text]  
  • Hannah, B. P., Cairns, T. M., Bender, F. C., Whitbeck, J. C., Lou, H., Eisenberg, R. J., Cohen, G. H. (2009). Herpes Simplex Virus Glycoprotein B Associates with Target Membranes via Its Fusion Loops. J. Virol. 83: 6825-6836 [Abstract] [Full Text]  
  • Aubert, M., Yoon, M., Sloan, D. D., Spear, P. G., Jerome, K. R. (2009). The Virological Synapse Facilitates Herpes Simplex Virus Entry into T Cells. J. Virol. 83: 6171-6183 [Abstract] [Full Text]  
  • Arii, J., Uema, M., Morimoto, T., Sagara, H., Akashi, H., Ono, E., Arase, H., Kawaguchi, Y. (2009). Entry of Herpes Simplex Virus 1 and Other Alphaherpesviruses via the Paired Immunoglobulin-Like Type 2 Receptor {alpha}. J. Virol. 83: 4520-4527 [Abstract] [Full Text]  
  • Uchida, H., Shah, W. A., Ozuer, A., Frampton, A. R. Jr., Goins, W. F., Grandi, P., Cohen, J. B., Glorioso, J. C. (2009). Generation of Herpesvirus Entry Mediator (HVEM)-Restricted Herpes Simplex Virus Type 1 Mutant Viruses: Resistance of HVEM-Expressing Cells and Identification of Mutations That Rescue Nectin-1 Recognition. J. Virol. 83: 2951-2961 [Abstract] [Full Text]  
  • Akkarawongsa, R., Pocaro, N. E., Case, G., Kolb, A. W., Brandt, C. R. (2009). Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection. Antimicrob. Agents Chemother. 53: 987-996 [Abstract] [Full Text]  
  • Kato, A., Arii, J., Shiratori, I., Akashi, H., Arase, H., Kawaguchi, Y. (2009). Herpes Simplex Virus 1 Protein Kinase Us3 Phosphorylates Viral Envelope Glycoprotein B and Regulates Its Expression on the Cell Surface. J. Virol. 83: 250-261 [Abstract] [Full Text]  
  • Vanarsdall, A. L., Ryckman, B. J., Chase, M. C., Johnson, D. C. (2008). Human Cytomegalovirus Glycoproteins gB and gH/gL Mediate Epithelial Cell-Cell Fusion When Expressed either in cis or in trans. J. Virol. 82: 11837-11850 [Abstract] [Full Text]  
  • Ryckman, B. J., Chase, M. C., Johnson, D. C. (2008). HCMV gH/gL/UL128-131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptors. Proc. Natl. Acad. Sci. USA 105: 14118-14123 [Abstract] [Full Text]  
  • Pinna, D., Oreste, P., Coradin, T., Kajaste-Rudnitski, A., Ghezzi, S., Zoppetti, G., Rotola, A., Argnani, R., Poli, G., Manservigi, R., Vicenzi, E. (2008). Inhibition of Herpes Simplex Virus Types 1 and 2 In Vitro Infection by Sulfated Derivatives of Escherichia coli K5 Polysaccharide. Antimicrob. Agents Chemother. 52: 3078-3084 [Abstract] [Full Text]  
  • Aizaki, H., Morikawa, K., Fukasawa, M., Hara, H., Inoue, Y., Tani, H., Saito, K., Nishijima, M., Hanada, K., Matsuura, Y., Lai, M. M. C., Miyamura, T., Wakita, T., Suzuki, T. (2008). Critical Role of Virion-Associated Cholesterol and Sphingolipid in Hepatitis C Virus Infection. J. Virol. 82: 5715-5724 [Abstract] [Full Text]  
  • Girgis, N. M., DeHaven, B. C., Fan, X., Viner, K. M., Shamim, M., Isaacs, S. N. (2008). Cell Surface Expression of the Vaccinia Virus Complement Control Protein Is Mediated by Interaction with the Viral A56 Protein and Protects Infected Cells from Complement Attack. J. Virol. 82: 4205-4214 [Abstract] [Full Text]  
  • Patrone, M., Secchi, M., Bonaparte, E., Milanesi, G., Gallina, A. (2007). Cytomegalovirus UL131-128 Products Promote gB Conformational Transition and gB-gH Interaction during Entry into Endothelial Cells. J. Virol. 81: 11479-11488 [Abstract] [Full Text]  
  • Hambleton, S., Steinberg, S. P., Gershon, M. D., Gershon, A. A. (2007). Cholesterol Dependence of Varicella-Zoster Virion Entry into Target Cells. J. Virol. 81: 7548-7558 [Abstract] [Full Text]  
  • Hannah, B. P., Heldwein, E. E., Bender, F. C., Cohen, G. H., Eisenberg, R. J. (2007). Mutational Evidence of Internal Fusion Loops in Herpes Simplex Virus Glycoprotein B. J. Virol. 81: 4858-4865 [Abstract] [Full Text]  
  • Teuton, J. R., Brandt, C. R. (2007). Sialic Acid on Herpes Simplex Virus Type 1 Envelope Glycoproteins Is Required for Efficient Infection of Cells. J. Virol. 81: 3731-3739 [Abstract] [Full Text]  
  • Bender, F. C., Samanta, M., Heldwein, E. E., de Leon, M. P., Bilman, E., Lou, H., Whitbeck, J. C., Eisenberg, R. J., Cohen, G. H. (2007). Antigenic and Mutational Analyses of Herpes Simplex Virus Glycoprotein B Reveal Four Functional Regions. J. Virol. 81: 3827-3841 [Abstract] [Full Text]  
  • Crim, R. L., Audet, S. A., Feldman, S. A., Mostowski, H. S., Beeler, J. A. (2007). Identification of Linear Heparin-Binding Peptides Derived from Human Respiratory Syncytial Virus Fusion Glycoprotein That Inhibit Infectivity. J. Virol. 81: 261-271 [Abstract] [Full Text]  
  • 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]  
  • Whitbeck, J. C., Zuo, Y., Milne, R. S. B., Cohen, G. H., Eisenberg, R. J. (2006). Stable Association of Herpes Simplex Virus with Target Membranes Is Triggered by Low pH in the Presence of the gD Receptor, HVEM.. J. Virol. 80: 3773-3780 [Abstract] [Full Text]  
  • Li, W., Minova-Foster, T. J., Norton, D. D., Muggeridge, M. I. (2006). Identification of functional domains in herpes simplex virus 2 glycoprotein B.. J. Virol. 80: 3792-3800 [Abstract] [Full Text]  
  • Kwon, H., Bai, Q., Baek, H.-J., Felmet, K., Burton, E. A., Goins, W. F., Cohen, J. B., Glorioso, J. C. (2006). Soluble V Domain of Nectin-1/HveC Enables Entry of Herpes Simplex Virus Type 1 (HSV-1) into HSV-Resistant Cells by Binding to Viral Glycoprotein D. J. Virol. 80: 138-148 [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»