Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency

被引:59
作者
Ford, PW
Bryan, BA
Dyson, OF
Weidner, DA
Chintalgattu, V
Akula, SM [1 ]
机构
[1] E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC 27834 USA
[2] E Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC 27834 USA
关键词
D O I
10.1099/vir.0.81628-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. In vivo, the virus is found predominantly in the latent state. In vitro, 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.
引用
收藏
页码:1139 / 1144
页数:6
相关论文
共 33 条
  • [1] B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells
    Akula, SM
    Ford, PW
    Whitman, AG
    Hamden, KE
    Bryan, BA
    Cook, PP
    McCubrey, JA
    [J]. BLOOD, 2005, 105 (11) : 4516 - 4522
  • [2] Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection
    Akula, SM
    Ford, PW
    Whitman, AG
    Hamden, KE
    Shelton, JG
    McCubrey, JA
    [J]. ONCOGENE, 2004, 23 (30) : 5227 - 5241
  • [3] Integrin α3β1 (CD 49c/29) is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells
    Akula, SM
    Pramod, NP
    Wang, FZ
    Chandran, B
    [J]. CELL, 2002, 108 (03) : 407 - 419
  • [4] Human herpesvirus 8 envelope-associated glycoprotein B interacts with heparan sulfate-like moieties
    Akula, SM
    Pramod, NP
    Wang, FZ
    Chandran, B
    [J]. VIROLOGY, 2001, 284 (02) : 235 - 249
  • [5] 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
    An, FQ
    Compitello, N
    Horwitz, E
    Sramkoski, M
    Knudsen, ES
    Renne, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (05) : 3862 - 3874
  • [6] Identifying cellular genes crucial for the reactivation of Kaposi's sarcoma-associated herpesvirus latency
    Bryan, BA
    Dyson, OF
    Akula, SM
    [J]. JOURNAL OF GENERAL VIROLOGY, 2006, 87 : 519 - 529
  • [7] IDENTIFICATION OF HERPESVIRUS-LIKE DNA-SEQUENCES IN AIDS-ASSOCIATED KAPOSIS-SARCOMA
    CHANG, Y
    CESARMAN, E
    PESSIN, MS
    LEE, F
    CULPEPPER, J
    KNOWLES, DM
    MOORE, PS
    [J]. SCIENCE, 1994, 266 (5192) : 1865 - 1869
  • [8] COOK SD, 1991, INVEST OPHTH VIS SCI, V32, P1558
  • [9] Role of protein kinase Cδ in reactivation of Kaposi's sarcoma-associated herpesvirus
    Deutsch, E
    Cohen, A
    Kazimirsky, G
    Dovrat, S
    Rubinfeld, H
    Brodie, C
    Sarid, R
    [J]. JOURNAL OF VIROLOGY, 2004, 78 (18) : 10187 - 10192
  • [10] Biology of Kaposi's sarcoma
    Ensoli, B
    Sgadari, C
    Barillari, G
    Sirianni, MC
    Stürzl, M
    Monini, P
    [J]. EUROPEAN JOURNAL OF CANCER, 2001, 37 (10) : 1251 - 1269