1887

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is a lytic structural protein expressed on the envelope of mature virions and on the membrane of cells supporting lytic infection. In addition to this viral glycoprotein’s interaction with integrins via its RGD (Arg-Gly-Asp) motif, KSHV gB possesses a disintegrin-like domain (DLD), which binds integrins as well. Prior to this study, there has been minimal research involving the less common integrin-binding motif, DLD, of gB as it pertains to herpesvirus infection. By using phage display peptide library screening and molecular biology techniques, the DLD of KSHV gB was shown to interact specifically with non-RGD binding α9β1 integrins. Similarly, monitoring wild-type infection confirmed α9β1:DLD interactions to be critical to successful KSHV infection of human foreskin fibroblast (HFF) cells and human dermal microvascular endothelial cells (HMVEC-d) compared with 293 cells. To further demonstrate the importance of the DLD of gB in KSHV infection, two recombinant virus constructs were generated using a bacterial artificial chromosome (BAC) system harbouring the KSHV genome (BAC36): BAC36ΔD-KSHV (lacking a functionally intact DLD of gB and containing an introduced tetracycline cassette) and BAC36.T-KSHV (containing an intact DLD sequence and an introduced tetracycline cassette). Accordingly, BAC36ΔD-KSHV presented significantly lower infection rates in HFF and HMVEC-d cells compared with the comparable infection rates achieved by wild-type BAC36-KSHV and BAC36.T-KSHV. Thus, the present report has delineated a critical role for the DLD of gB in KSHV infection, which may lead to a broader knowledge regarding the sophisticated mechanisms utilized by virus-encoded structural proteins in KSHV entry and infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.066829-0
2014-08-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/8/1770.html?itemId=/content/journal/jgv/10.1099/vir.0.066829-0&mimeType=html&fmt=ahah

References

  1. Akula S. M., Pramod N. P., Wang F. Z., Chandran B.. ( 2001a; ). Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties. . Virology 284:, 235–249. [CrossRef] [PubMed]
    [Google Scholar]
  2. Akula S. M., Wang F. Z., Vieira J., Chandran B.. ( 2001b; ). Human herpesvirus 8 interaction with target cells involves heparan sulfate. . Virology 282:, 245–255. [CrossRef] [PubMed]
    [Google Scholar]
  3. Akula S. M., Pramod N. P., Wang F. Z., Chandran B.. ( 2002; ). Integrin α3β1 (CD 49c/29) is a cellular receptor for Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. . Cell 108:, 407–419. [CrossRef] [PubMed]
    [Google Scholar]
  4. Akula S. M., Ford P. W., Whitman A. G., Hamden K. E., Shelton J. G., McCubrey J. A.. ( 2004; ). Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection. . Oncogene 23:, 5227–5241. [CrossRef] [PubMed]
    [Google Scholar]
  5. Akula S. M., Ford P. W., Whitman A. G., Hamden K. E., Bryan B. A., Cook P. P., McCubrey J. A.. ( 2005; ). B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells. . Blood 105:, 4516–4522. [CrossRef] [PubMed]
    [Google Scholar]
  6. Andrews M. R., Czvitkovich S., Dassie E., Vogelaar C. F., Faissner A., Blits B., Gage F. H., ffrench-Constant C., Fawcett J. W.. ( 2009; ). α9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration. . J Neurosci 29:, 5546–5557. [CrossRef] [PubMed]
    [Google Scholar]
  7. Backovic M., Longnecker R., Jardetzky T. S.. ( 2009; ). Structure of a trimeric variant of the Epstein–Barr virus glycoprotein B. . Proc Natl Acad Sci U S A 106:, 2880–2885. [CrossRef] [PubMed]
    [Google Scholar]
  8. Bryan B. A., Dyson O. F., McCubrey J. A., Akula S. M.. ( 2005; ). Biology of Kaposi’s sarcoma-associated herpesvirus. . Front Biosci 10:, 2882–2891. [CrossRef] [PubMed]
    [Google Scholar]
  9. Chakraborty S., Veettil M. V., Chandran B.. ( 2012; ). Kaposi’s sarcoma associated herpesvirus entry into target cells. . Front Microbiol 3:, 6. [CrossRef] [PubMed]
    [Google Scholar]
  10. Chandran B.. ( 2010; ). Early events in Kaposi’s sarcoma-associated herpesvirus infection of target cells. . J Virol 84:, 2188–2199. [CrossRef] [PubMed]
    [Google Scholar]
  11. Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S.. ( 1994; ). Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. . Science 266:, 1865–1869. [CrossRef] [PubMed]
    [Google Scholar]
  12. Desiderio U. V., Zhu X., Evans J. P.. ( 2010; ). ADAM2 interactions with mouse eggs and cell lines expressing α4/α9 (ITGA4/ITGA9) integrins: implications for integrin-based adhesion and fertilization. . PLoS ONE 5:, e13744. [CrossRef] [PubMed]
    [Google Scholar]
  13. Dyson O. F., Traylen C. M., Akula S. M.. ( 2010; ). Cell membrane-bound Kaposi’s sarcoma-associated herpesvirus-encoded glycoprotein B promotes virus latency by regulating expression of cellular Egr-1. . J Biol Chem 285:, 37491–37502. [CrossRef] [PubMed]
    [Google Scholar]
  14. Dyson O. F., Walker L. R., Whitehouse A., Cook P. P., Akula S. M.. ( 2012; ). Resveratrol inhibits KSHV reactivation by lowering the levels of cellular EGR-1. . PLoS ONE 7:, e33364. [CrossRef] [PubMed]
    [Google Scholar]
  15. Eto K., Huet C., Tarui T., Kupriyanov S., Liu H. Z., Puzon-McLaughlin W., Zhang X. P., Sheppard D., Engvall E., Takada Y.. ( 2002; ). Functional classification of ADAMs based on a conserved motif for binding to integrin α9β1: implications for sperm-egg binding and other cell interactions. . J Biol Chem 277:, 17804–17810. [CrossRef] [PubMed]
    [Google Scholar]
  16. 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 U S A 101:, 15470–15475. [CrossRef] [PubMed]
    [Google Scholar]
  17. Feire A. L., Roy R. M., Manley K., Compton T.. ( 2010; ). The glycoprotein B disintegrin-like domain binds beta 1 integrin to mediate cytomegalovirus entry. . J Virol 84:, 10026–10037. [CrossRef] [PubMed]
    [Google Scholar]
  18. Garrigues H. J., Rubinchikova Y. E., Dipersio C. M., Rose T. M.. ( 2008; ). Integrin αVβ3 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. [CrossRef] [PubMed]
    [Google Scholar]
  19. Grange P. A., Gressier L., Williams J. F., Dyson O. F., Akula S. M., Dupin N.. ( 2012; ). Cloning a human saliva-derived peptide for preventing KSHV transmission. . J Invest Dermatol 132:, 1733–1735. [CrossRef] [PubMed]
    [Google Scholar]
  20. Hahn A., Birkmann A., Wies E., Dorer D., Mahr K., Stürzl 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. [CrossRef] [PubMed]
    [Google Scholar]
  21. Hahn A. S., Kaufmann J. K., Wies E., Naschberger E., Panteleev-Ivlev J., Schmidt K., Holzer A., Schmidt M., Chen J.. & other authors ( 2012; ). The ephrin receptor tyrosine kinase A2 is a cellular receptor for Kaposi’s sarcoma-associated herpesvirus. . Nat Med 18:, 961–966. [CrossRef] [PubMed]
    [Google Scholar]
  22. Hamden K. E., Whitman A. G., Ford P. W., Shelton J. G., McCubrey J. A., Akula S. M.. ( 2005; ). Raf and VEGF: emerging therapeutic targets in Kaposi’s sarcoma-associated herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic tumors. . Leukemia 19:, 18–26.[PubMed]
    [Google Scholar]
  23. Inoue N., Winter J., Lal R. B., Offermann M. K., Koyano S.. ( 2003; ). Characterization of entry mechanisms of human herpesvirus 8 by using an Rta-dependent reporter cell line. . J Virol 77:, 8147–8152. [CrossRef] [PubMed]
    [Google Scholar]
  24. Laskowski R. A., Gerick F., Thornton J. M.. ( 2009; ). The structural basis of allosteric regulation in proteins. . FEBS Lett 583:, 1692–1698. [CrossRef] [PubMed]
    [Google Scholar]
  25. Lu D., Scully M., Kakkar V., Lu X.. ( 2010; ). ADAM-15 disintegrin-like domain structure and function. . Toxins (Basel) 2:, 2411–2427. [CrossRef] [PubMed]
    [Google Scholar]
  26. Orend G., Chiquet-Ehrismann R.. ( 2006; ). Tenascin-C induced signaling in cancer. . Cancer Lett 244:, 143–163. [CrossRef] [PubMed]
    [Google Scholar]
  27. Rappocciolo G., Jenkins F. J., Hensler H. R., Piazza P., Jais M., Borowski L., Watkins S. C., Rinaldo C. R. Jr. ( 2006; ). DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. . J Immunol 176:, 1741–1749. [CrossRef] [PubMed]
    [Google Scholar]
  28. Rappocciolo G., Hensler H. R., Jais M., Reinhart T. A., Pegu A., Jenkins F. J., Rinaldo C. R.. ( 2008; ). Human herpesvirus 8 infects and replicates in primary cultures of activated B lymphocytes through DC-SIGN. . J Virol 82:, 4793–4806. [CrossRef] [PubMed]
    [Google Scholar]
  29. Russo J. J., Bohenzky R. A., Chien M. C., Chen J., Yan M., Maddalena D., Parry J. P., Peruzzi D., Edelman I. S.. & other authors ( 1996; ). Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). . Proc Natl Acad Sci U S A 93:, 14862–14867. [CrossRef] [PubMed]
    [Google Scholar]
  30. 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 (αVβ5, αVβ3, and α3β1) 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. [CrossRef] [PubMed]
    [Google Scholar]
  31. Vieira J., O’Hearn P., Kimball L., Chandran B., Corey L.. ( 2001; ). Activation of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) lytic replication by human cytomegalovirus. . J Virol 75:, 1378–1386. [CrossRef] [PubMed]
    [Google Scholar]
  32. Vlahakis N. E., Young B. A., Atakilit A., Sheppard D.. ( 2005; ). The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin α9β1. . J Biol Chem 280:, 4544–4552. [CrossRef] [PubMed]
    [Google Scholar]
  33. Wang F. Z., Akula S. M., Sharma-Walia N., Zeng L., Chandran B.. ( 2003; ). Human herpesvirus 8 envelope glycoprotein B mediates cell adhesion via its RGD sequence. . J Virol 77:, 3131–3147. [CrossRef] [PubMed]
    [Google Scholar]
  34. Wolfsberg T. G., Straight P. D., Gerena R. L., Huovila A. P., Primakoff P., Myles D. G., White J. M.. ( 1995; ). ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain. . Dev Biol 169:, 378–383. [CrossRef] [PubMed]
    [Google Scholar]
  35. Yakushko Y., Hackmann C., Günther T., Rückert J., Henke M., Koste L., Alkharsah K., Bohne J., Grundhoff A.. & other authors ( 2011; ). Kaposi’s sarcoma-associated herpesvirus bacterial artificial chromosome contains a duplication of a long unique-region fragment within the terminal repeat region. . J Virol 85:, 4612–4617. [CrossRef] [PubMed]
    [Google Scholar]
  36. Yokosaki Y., Palmer E. L., Prieto A. L., Crossin K. L., Bourdon M. A., Pytela R., Sheppard D.. ( 1994; ). The integrin alpha 9 beta 1 mediates cell attachment to a non-RGD site in the third fibronectin type III repeat of tenascin. . J Biol Chem 269:, 26691–26696.[PubMed]
    [Google Scholar]
  37. Young B. A., Taooka Y., Liu S., Askins K. J., Yokosaki Y., Thomas S. M., Sheppard D.. ( 2001; ). The cytoplasmic domain of the integrin α9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration in a paxillin-independent manner. . Mol Biol Cell 12:, 3214–3225. [CrossRef] [PubMed]
    [Google Scholar]
  38. Zhang W., Gao S. J.. ( 2012; ). Exploitation of cellular cytoskeletons and signaling pathways for cell entry by Kaposi’s sarcoma-associated herpesvirus and the closely related rhesus rhadinovirus. . Pathogens 1:, 102–127. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.066829-0
Loading
/content/journal/jgv/10.1099/vir.0.066829-0
Loading

Data & Media loading...

Supplements

Supplementary Material 

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error