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 Sharma-Walia, N.
Right arrow Articles by Chandran, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma-Walia, N.
Right arrow Articles by Chandran, B.

 Previous Article  |  Next Article 

Journal of Virology, April 2004, p. 4207-4223, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4207-4223.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 Envelope Glycoprotein gB Induces the Integrin-Dependent Focal Adhesion Kinase-Src-Phosphatidylinositol 3-Kinase-Rho GTPase Signal Pathways and Cytoskeletal Rearrangements

Neelam Sharma-Walia, Pramod P. Naranatt, Harinivas H. Krishnan, Ling Zeng, and Bala Chandran*

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160

Received 13 August 2003/ Accepted 17 December 2003

Human herpesvirus 8 (HHV-8; Kaposi's sarcoma-associated herpesvirus) envelope glycoprotein gB possesses an RGD motif, interacts with {alpha}3ß1 integrin, and uses it as one of the entry receptors. HHV-8 induces the integrin-dependent focal adhesion kinase (FAK), a critical step in the outside-in signaling pathways necessary for the subsequent phosphorylation of other cellular kinases, cytoskeletal rearrangements, and other functions. As an initial step toward deciphering the role of HHV-8 gB-integrin interaction in infection, signal pathways induced by gB were examined. A truncated form of gB without the transmembrane and carboxyl domains (gB{Delta}TM), a gB{Delta}TM mutant form (gB{Delta}TM-RGA) with an RGD-to-RGA mutation, and inhibitors of cellular kinases were used. HHV-8 gB{Delta}TM, but not gB{Delta}TM-RGA, induced FAK phosphorylation in target cells, which was in part dependent on the presence of {alpha}3ß1 integrin. FAK was critical for the subsequent phosphorylation of Src by gB{Delta}TM, and Src induction was essential for the phosphorylation of phosphatidylinositol 3-kinase (PI-3K). HHV-8 gB{Delta}TM-induced PI-3K was essential for the induction of RhoA and Cdc42 Rho GTPases that was accompanied by the cytoskeletal rearrangements. These gB-induced morphological changes were inhibited by the PI-3K inhibitors. Ezrin, one of the essential elements required to cross-link the actin cytoskeleton with the plasma membrane and to induce the morphological changes, was induced by the Rho GTPases. Inhibition of cellular tyrosine kinases by the brief treatment of cells with 4',5,7-trihydroxyisoflavone (genistein) blocked the entry of HHV-8 into target cells. These findings suggest that, independently of other viral glycoproteins and via its RGD motif, HHV-8 gB induces integrin-dependent pre-existing FAK-Src-PI-3K-Rho GTPase kinases. Since these signal pathways play vital roles in host cell endocytosis and movement of particulate materials in the cytoplasm, the early stages of HHV-8 gB interaction with host cells may provide a very conducive environment for the successful infection of target cells.

* Corresponding author. Mailing address: Department of Microbiology, Molecular Genetics and Immunology, Mail Stop 3029, The University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160. Phone: (913) 588-7043. Fax: (913) 588-7295. E-mail: bchandra{at}kumc.edu.

Journal of Virology, April 2004, p. 4207-4223, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.4207-4223.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Raghu, H., Sharma-Walia, N., Veettil, M. V., Sadagopan, S., Chandran, B. (2009). Kaposi's Sarcoma-Associated Herpesvirus Utilizes an Actin Polymerization-Dependent Macropinocytic Pathway To Enter Human Dermal Microvascular Endothelial and Human Umbilical Vein Endothelial Cells. J. Virol. 83: 4895-4911 [Abstract] [Full Text]  
  • Sadagopan, S., Sharma-Walia, N., Veettil, M. V., Bottero, V., Levine, R., Vart, R. J., Chandran, B. (2009). Kaposi's Sarcoma-Associated Herpesvirus Upregulates Angiogenin during Infection of Human Dermal Microvascular Endothelial Cells, Which Induces 45S rRNA Synthesis, Antiapoptosis, Cell Proliferation, Migration, and Angiogenesis. J. Virol. 83: 3342-3364 [Abstract] [Full Text]  
  • Lyman, M. G., Enquist, L. W. (2009). Herpesvirus Interactions with the Host Cytoskeleton. J. Virol. 83: 2058-2066 [Full Text]  
  • Hahn, A., Birkmann, A., Wies, E., Dorer, D., Mahr, K., Sturzl, M., Titgemeyer, F., Neipel, F. (2009). Kaposi's Sarcoma-Associated Herpesvirus gH/gL: Glycoprotein Export and Interaction with Cellular Receptors. J. Virol. 83: 396-407 [Abstract] [Full Text]  
  • Veettil, M. V., Sadagopan, S., Sharma-Walia, N., Wang, F.-Z., Raghu, H., Varga, L., Chandran, B. (2008). Kaposi's Sarcoma-Associated Herpesvirus Forms a Multimolecular Complex of Integrins ({alpha}V{beta}5, {alpha}V{beta}3, and {alpha}3{beta}1) and CD98-xCT during Infection of Human Dermal Microvascular Endothelial Cells, and CD98-xCT Is Essential for the Postentry Stage of Infection. J. Virol. 82: 12126-12144 [Abstract] [Full Text]  
  • Xiao, Y. Q., Freire-de-Lima, C. G., Schiemann, W. P., Bratton, D. L., Vandivier, R. W., Henson, P. M. (2008). Transcriptional and Translational Regulation of TGF-{beta} Production in Response to Apoptotic Cells. J. Immunol. 181: 3575-3585 [Abstract] [Full Text]  
  • Garrigues, H. J., Rubinchikova, Y. E., DiPersio, C. M., Rose, T. M. (2008). Integrin {alpha}V 3 Binds to the RGD Motif of Glycoprotein B of Kaposi's Sarcoma-Associated Herpesvirus and Functions as an RGD-Dependent Entry Receptor. J. Virol. 82: 1570-1580 [Abstract] [Full Text]  
  • Swanson, K. A., Crane, D. D., Caldwell, H. D. (2007). Chlamydia trachomatis Species-Specific Induction of Ezrin Tyrosine Phosphorylation Functions in Pathogen Entry. Infect. Immun. 75: 5669-5677 [Abstract] [Full Text]  
  • Frampton, A. R. Jr., Stolz, D. B., Uchida, H., Goins, W. F., Cohen, J. B., Glorioso, J. C. (2007). Equine Herpesvirus 1 Enters Cells by Two Different Pathways, and Infection Requires the Activation of the Cellular Kinase ROCK1. J. Virol. 81: 10879-10889 [Abstract] [Full Text]  
  • Raghu, H., Sharma-Walia, N., Veettil, M. V., Sadagopan, S., Caballero, A., Sivakumar, R., Varga, L., Bottero, V., Chandran, B. (2007). Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Induced Phosphatidylinositol 3-Kinase and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry. J. Virol. 81: 7941-7959 [Abstract] [Full Text]  
  • Sadagopan, S., Sharma-Walia, N., Veettil, M. V., Raghu, H., Sivakumar, R., Bottero, V., Chandran, B. (2007). Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained NF-{kappa}B Activation during De Novo Infection of Primary Human Dermal Microvascular Endothelial Cells That Is Essential for Viral Gene Expression. J. Virol. 81: 3949-3968 [Abstract] [Full Text]  
  • Bentley, J. K., Newcomb, D. C., Goldsmith, A. M., Jia, Y., Sajjan, U. S., Hershenson, M. B. (2007). Rhinovirus Activates Interleukin-8 Expression via a Src/p110{beta} Phosphatidylinositol 3-Kinase/Akt Pathway in Human Airway Epithelial Cells. J. Virol. 81: 1186-1194 [Abstract] [Full Text]  
  • Veettil, M. V., Sharma-Walia, N., Sadagopan, S., Raghu, H., Sivakumar, R., Naranatt, P. P., Chandran, B. (2006). RhoA-GTPase Facilitates Entry of Kaposi's Sarcoma-Associated Herpesvirus into Adherent Target Cells in a Src-Dependent Manner. J. Virol. 80: 11432-11446 [Abstract] [Full Text]  
  • Perry, S. T., Compton, T. (2006). Kaposi's Sarcoma-Associated Herpesvirus Virions Inhibit Interferon Responses Induced by Envelope Glycoprotein gpK8.1. J. Virol. 80: 11105-11114 [Abstract] [Full Text]  
  • Pellinen, T., Ivaska, J. (2006). Integrin traffic.. J. Cell Sci. 119: 3723-3731 [Abstract] [Full Text]  
  • Sharma-Walia, N., Raghu, H., Sadagopan, S., Sivakumar, R., Veettil, M. V., Naranatt, P. P., Smith, M. M., Chandran, B. (2006). Cyclooxygenase 2 Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during In Vitro Infection of Target Cells Plays a Role in the Maintenance of Latent Viral Gene Expression.. J. Virol. 80: 6534-6552 [Abstract] [Full Text]  
  • Krishnan, H. H., Sharma-Walia, N., Streblow, D. N., Naranatt, P. P., Chandran, B. (2006). Focal Adhesion Kinase Is Critical for Entry of Kaposi's Sarcoma-Associated Herpesvirus into Target Cells. J. Virol. 80: 1167-1180 [Abstract] [Full Text]  
  • Xie, J., Pan, H., Yoo, S., Gao, S.-J. (2005). Kaposi's Sarcoma-Associated Herpesvirus Induction of AP-1 and Interleukin 6 during Primary Infection Mediated by Multiple Mitogen-Activated Protein Kinase Pathways. J. Virol. 79: 15027-15037 [Abstract] [Full Text]  
  • Cheshenko, N., Liu, W., Satlin, L. M., Herold, B. C. (2005). Focal Adhesion Kinase Plays a Pivotal Role in Herpes Simplex Virus Entry. J. Biol. Chem. 280: 31116-31125 [Abstract] [Full Text]  
  • Krishnan, H. H., Sharma-Walia, N., Zeng, L., Gao, S.-J., Chandran, B. (2005). Envelope Glycoprotein gB of Kaposi's Sarcoma-Associated Herpesvirus Is Essential for Egress from Infected Cells. J. Virol. 79: 10952-10967 [Abstract] [Full Text]  
  • Urbinati, C., Bugatti, A., Giacca, M., Schlaepfer, D., Presta, M., Rusnati, M. (2005). {alpha}v{beta}3-integrin-dependent activation of focal adhesion kinase mediates NF-{kappa}B activation and motogenic activity by HIV-1 Tat in endothelial cells. J. Cell Sci. 118: 3949-3958 [Abstract] [Full Text]  
  • Sharma-Walia, N., Krishnan, H. H., Naranatt, P. P., Zeng, L., Smith, M. S., Chandran, B. (2005). ERK1/2 and MEK1/2 Induced by Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Early during Infection of Target Cells Are Essential for Expression of Viral Genes and for Establishment of Infection. J. Virol. 79: 10308-10329 [Abstract] [Full Text]  
  • Zhang, X., Wang, J. F., Chandran, B., Persaud, K., Pytowski, B., Fingeroth, J., Groopman, J. E. (2005). Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection. J. Biol. Chem. 280: 26216-26224 [Abstract] [Full Text]  
  • Bechtel, J. T., Winant, R. C., Ganem, D. (2005). Host and Viral Proteins in the Virion of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 79: 4952-4964 [Abstract] [Full Text]  
  • Naranatt, P. P., Krishnan, H. H., Smith, M. S., Chandran, B. (2005). Kaposi's Sarcoma-Associated Herpesvirus Modulates Microtubule Dynamics via RhoA-GTP-Diaphanous 2 Signaling and Utilizes the Dynein Motors To Deliver Its DNA to the Nucleus. J. Virol. 79: 1191-1206 [Abstract] [Full Text]  
  • Feire, A. L., Koss, H., Compton, T. (2004). Cellular integrins function as entry receptors for human cytomegalovirus via a highly conserved disintegrin-like domain. Proc. Natl. Acad. Sci. USA 101: 15470-15475 [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»