1887

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. KSHV infection of cells produces both latent and lytic cycles of infection. , the virus is found predominantly in the latent state. , a lytic infection can be induced in KSHV-infected cells by treating with phorbol ester (TPA). However, the exact signalling events that lead to the reactivation of KSHV lytic infection are still elusive. Here, a role is demonstrated for B-Raf/MEK/ERK signalling in TPA-induced reactivation of KSHV latent infection. Inhibiting MEK/ERK signalling by using MEK-specific inhibitors decreased expression of the TPA-induced KSHV lytic-cycle gene ORF8. Transfection of BCBL-1 cells with B-Raf small interfering RNA inhibited TPA-induced KSHV lytic infection significantly. Additionally, overexpression of MEK1 induced a lytic cycle of KSHV infection in BCBL-1 cells. The significance of these findings in understanding the biology of KSHV-associated pathogenesis is discussed.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81628-0
2006-05-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/5/1139.html?itemId=/content/journal/jgv/10.1099/vir.0.81628-0&mimeType=html&fmt=ahah

References

  1. Akula S. M., Pramod N. P., Wang F.-Z., Chandran B. 2001; Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties. Virology 284:235–249 [CrossRef]
    [Google Scholar]
  2. Akula S. M., Pramod N. P., Wang F.-Z., Chandran B. 2002; Integrin α 3 β 1 (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]
    [Google Scholar]
  3. 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]
    [Google Scholar]
  4. 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]
    [Google Scholar]
  5. An F.-Q., Compitello N., Horwitz E., Sramkoski M., Knudsen E. S., Renne R. 2005; The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest. J Biol Chem 280:3862–3874 [CrossRef]
    [Google Scholar]
  6. Bryan B. A., Dyson O. F., Akula S. M. 2006; Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency. J Gen Virol 87:519–529 [CrossRef]
    [Google Scholar]
  7. 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]
    [Google Scholar]
  8. Cook S. D., Paveloff M. J., Doucet J. J., Cottingham A. J., Sedarati F., Hill J. M. 1991; Ocular herpes simplex virus reactivation in mice latently infected with latency-associated transcript mutants. Invest Ophthalmol Vis Sci 32:1558–1561
    [Google Scholar]
  9. Deutsch E., Cohen A., Kazimirsky G., Dovrat S., Rubinfeld H., Brodie C., Sarid R. 2004; Role of protein kinase C δ in reactivation of Kaposi's sarcoma-associated herpesvirus. J Virol 78:10187–10192 [CrossRef]
    [Google Scholar]
  10. Ensoli B., Sgadari C., Barillari G., Sirianni M. C., Stürzl M., Monini P. 2001; Biology of Kaposi's sarcoma. Eur J Cancer 37:1251–1269 [CrossRef]
    [Google Scholar]
  11. Faris M., Ensoli B., Kokot N., Nel A. E. 1998; Inflammatory cytokines induce the expression of basic fibroblast growth factor (bFGF) isoforms required for the growth of Kaposi's sarcoma and endothelial cells through the activation of AP-1 response elements in the bFGF promoter. AIDS 12:19–27 [CrossRef]
    [Google Scholar]
  12. Fenton M., Sinclair A. J. 1999; Divergent requirements for the MAPKERK signal transduction pathway during initial virus infection of quiescent primary B cells and disruption of Epstein-Barr virus latency by phorbol esters. J Virol 73:8913–8916
    [Google Scholar]
  13. Friborg J. Jr, Kong W.-P., Hottiger M. O., Nabel G. J. 1999; p53 inhibition by the LANA protein of KSHV protects against cell death. Nature 402:889–894
    [Google Scholar]
  14. Fujimuro M., Liu J., Zhu J., Yokosawa H., Hayward S. D. 2005; Regulation of the interaction between glycogen synthase kinase 3 and the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen. J Virol 79:10429–10441 [CrossRef]
    [Google Scholar]
  15. Gao X., Ikuta K., Tajima M., Sairenji T. 2001; 12- O -Tetradecanoylphorbol-13-acetate induces Epstein–Barr virus reactivation via NF- κ B and AP-1 as regulated by protein kinase C and mitogen-activated protein kinase. Virology 286:91–99 [CrossRef]
    [Google Scholar]
  16. Giri R. K., Selvaraj S. K., Kalra V. K. 2003; Amyloid peptide-induced cytokine and chemokine expression in THP-1 monocytes is blocked by small inhibitory RNA duplexes for early growth response-1 messenger RNA. J Immunol 170:5281–5294 [CrossRef]
    [Google Scholar]
  17. Hamden K. E., Ford P. W., Whitman A. G., Dyson O. F., Cheng S.-Y., McCubrey J. A., Akula S. M. 2004; Raf-induced vascular endothelial growth factor augments Kaposi's sarcoma-associated herpesvirus infection. J Virol 78:13381–13390 [CrossRef]
    [Google Scholar]
  18. Jang B.-C., Jung T.-Y., Paik J.-H., Kwon Y.-K., Shin S.-W., Kim S.-P., Ha J.-S., Suh M.-H., Suh S.-I. 2005; Tetradecanoyl phorbol acetate induces expression of Toll-like receptor 2 in U937 cells: involvement of PKC, ERK, and NF- κ B. Biochem Biophys Res Commun 328:70–77 [CrossRef]
    [Google Scholar]
  19. Jenner R. G., Albà M. M., Boshoff C., Kellam P. 2001; Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75:891–902 [CrossRef]
    [Google Scholar]
  20. Jordan M. C., Jordan G. W., Stevens J. G., Miller G. 1984; Latent herpesviruses of humans. Ann Intern Med 100:866–880 [CrossRef]
    [Google Scholar]
  21. Karasarides M., Chiloeches A., Hayward R. & 9 other authors 2004; B-RAF is a therapeutic target in melanoma. Oncogene 23:6292–6298 [CrossRef]
    [Google Scholar]
  22. Lan K., Kuppers D. A., Verma S. C., Robertson E. S. 2004; Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency. J Virol 78:6585–6594 [CrossRef]
    [Google Scholar]
  23. Man K., Ng K. T., Lee T. K., Lo C. M., Sun C. K., Li X. L., Zhao Y., Ho J. W., Fan S. T. 2005; FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers. Am J Transplant 5:40–49 [CrossRef]
    [Google Scholar]
  24. Marquardt B., Frith D., Stabel S. 1994; Signalling from TPA to MAP kinase requires protein kinase C, raf and MEK: reconstitution of the signalling pathway in vitro. Oncogene 9:3213–3218
    [Google Scholar]
  25. Matsubara M., Tamura T., Ohmori K., Hasegawa K. 2005; Histamine H1 receptor antagonist blocks histamine-induced proinflammatory cytokine production through inhibition of Ca2+-dependent protein kinase C, Raf/MEK/ERK and IKK/I κ B/NF- κ B signal cascades. Biochem Pharmacol 69:433–449 [CrossRef]
    [Google Scholar]
  26. Nakayama K., Ota Y., Okugawa S., Ise N., Kitazawa T., Tsukada K., Kawada M., Yanagimoto S., Kimura S. 2003; Raf1 plays a pivotal role in lipopolysaccharide-induced activation of dendritic cells. Biochem Biophys Res Commun 308:353–360 [CrossRef]
    [Google Scholar]
  27. O'Neill E., Kolch W. 2004; Conferring specificity on the ubiquitous Raf/MEK signalling pathway. Br J Cancer 90:283–288 [CrossRef]
    [Google Scholar]
  28. Radkov S. A., Kellam P., Boshoff C. 2000; The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma–E2F pathway and with the oncogene Hras transforms primary rat cells. Nat Med 6:1121–1127 [CrossRef]
    [Google Scholar]
  29. Renne R., Zhong W., Herndier B., McGrath M., Abbey N., Kedes D., Ganem D. 1996; Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med 2:342–346 [CrossRef]
    [Google Scholar]
  30. Satoh T., Hoshikawa Y., Satoh Y., Kurata T., Sairenji T. 1999; The interaction of mitogen-activated protein kinases to Epstein-Barr virus activation in Akata cells. Virus Genes 18:57–64 [CrossRef]
    [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]
    [Google Scholar]
  32. Yang X., Chen Y., Gabuzda D. 1999; ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF- κ B. J Biol Chem 274:27981–27988 [CrossRef]
    [Google Scholar]
  33. Yang T.-Y., Chen S.-C., Leach M. W. & 8 other authors 2000; Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma. J Exp Med 191:445–454 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81628-0
Loading
/content/journal/jgv/10.1099/vir.0.81628-0
Loading

Data & Media loading...

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