Tags

Type your tag names separated by a space and hit enter

In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2.
Int J Cancer. 2005 Mar 01; 113(6):937-45.IJ

Abstract

In about 50% of classical Hodgkin lymphomas, the Hodgkin/Reed Sternberg (H/RS) cells carry Epstein-Barr virus (EBV). The viral gene expression in these cells is restricted to EBNA-1, EBERs, LMP-1 and LMP-2 (type II latency). The origin of H/RS cells was defined as crippled germinal center B cells that escaped apoptosis. In spite of numerous attempts, only few typical Hodgkin lymphoma (HL) lines have been established. This suggests that the cells require survival factors that they receive in the in vivo microenvironment. If EBV is expected to drive the cells for growth in culture, the absence of EBNA-2 may explain the incapacity of H/RS cells for in vitro proliferation. In EBV carrying B lymphocytes, functional EBNA-2 and LMP-1 proteins are required for in vitro growth. For analysis of the interaction between EBV and the H/RS cells, we infected the CD21-positive HL line KMH2 with the B958 and Akata viral strains. Only EBNA-1 expression was detected in a few cells in spite of the fact that all cells could be infected. Using a neomycin-resistance-tagged recombinant EBV strain (Akata-Neo) we established an EBV-positive subline that was carried on selective medium. In contrast to the type II EBV expression pattern of H/RS cells in vivo, the KMH2 EBV cells did not express LMP-1. The EBV expression pattern could be modified in this type I subline. LMP-1 could be induced by the histone deacetylase inhibitors TSA and n-butyrate, by 5-AzaC, a demethylating agent, and by phorbol ester. None of these treatments induced EBNA-2. Importantly, exposure to CD40 ligand and IL-4 induced LMP-1 without EBNA-2 expression and lytic replication. The KMH2 EBV cells expressed LMP-2A, but not LMP-2B mRNAs. This result is highly relevant for the type II expression pattern of H/RS cells in vivo, since these stimuli can be provided by the surrounding activated T lymphocytes.

Authors+Show Affiliations

Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. kis.lorand.levente@mtc.ki.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15514968

Citation

Kis, Loránd L., et al. "In Vitro EBV-infected Subline of KMH2, Derived From Hodgkin Lymphoma, Expresses Only EBNA-1, While CD40 Ligand and IL-4 Induce LMP-1 but Not EBNA-2." International Journal of Cancer, vol. 113, no. 6, 2005, pp. 937-45.
Kis LL, Nishikawa J, Takahara M, et al. In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2. Int J Cancer. 2005;113(6):937-45.
Kis, L. L., Nishikawa, J., Takahara, M., Nagy, N., Matskova, L., Takada, K., Elmberger, P. G., Ohlsson, A., Klein, G., & Klein, E. (2005). In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2. International Journal of Cancer, 113(6), 937-45.
Kis LL, et al. In Vitro EBV-infected Subline of KMH2, Derived From Hodgkin Lymphoma, Expresses Only EBNA-1, While CD40 Ligand and IL-4 Induce LMP-1 but Not EBNA-2. Int J Cancer. 2005 Mar 1;113(6):937-45. PubMed PMID: 15514968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2. AU - Kis,Loránd L, AU - Nishikawa,Jun, AU - Takahara,Miki, AU - Nagy,Noémi, AU - Matskova,Liudmila, AU - Takada,Kenzo, AU - Elmberger,P Göran, AU - Ohlsson,Ann, AU - Klein,George, AU - Klein,Eva, PY - 2004/10/30/pubmed PY - 2005/3/8/medline PY - 2004/10/30/entrez SP - 937 EP - 45 JF - International journal of cancer JO - Int J Cancer VL - 113 IS - 6 N2 - In about 50% of classical Hodgkin lymphomas, the Hodgkin/Reed Sternberg (H/RS) cells carry Epstein-Barr virus (EBV). The viral gene expression in these cells is restricted to EBNA-1, EBERs, LMP-1 and LMP-2 (type II latency). The origin of H/RS cells was defined as crippled germinal center B cells that escaped apoptosis. In spite of numerous attempts, only few typical Hodgkin lymphoma (HL) lines have been established. This suggests that the cells require survival factors that they receive in the in vivo microenvironment. If EBV is expected to drive the cells for growth in culture, the absence of EBNA-2 may explain the incapacity of H/RS cells for in vitro proliferation. In EBV carrying B lymphocytes, functional EBNA-2 and LMP-1 proteins are required for in vitro growth. For analysis of the interaction between EBV and the H/RS cells, we infected the CD21-positive HL line KMH2 with the B958 and Akata viral strains. Only EBNA-1 expression was detected in a few cells in spite of the fact that all cells could be infected. Using a neomycin-resistance-tagged recombinant EBV strain (Akata-Neo) we established an EBV-positive subline that was carried on selective medium. In contrast to the type II EBV expression pattern of H/RS cells in vivo, the KMH2 EBV cells did not express LMP-1. The EBV expression pattern could be modified in this type I subline. LMP-1 could be induced by the histone deacetylase inhibitors TSA and n-butyrate, by 5-AzaC, a demethylating agent, and by phorbol ester. None of these treatments induced EBNA-2. Importantly, exposure to CD40 ligand and IL-4 induced LMP-1 without EBNA-2 expression and lytic replication. The KMH2 EBV cells expressed LMP-2A, but not LMP-2B mRNAs. This result is highly relevant for the type II expression pattern of H/RS cells in vivo, since these stimuli can be provided by the surrounding activated T lymphocytes. SN - 0020-7136 UR - https://www.unboundmedicine.com/medline/citation/15514968/In_vitro_EBV_infected_subline_of_KMH2_derived_from_Hodgkin_lymphoma_expresses_only_EBNA_1_while_CD40_ligand_and_IL_4_induce_LMP_1_but_not_EBNA_2_ L2 - https://doi.org/10.1002/ijc.20654 DB - PRIME DP - Unbound Medicine ER -