IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines.
EBV-positive nasopharyngeal carcinoma and Hodgkin, T, and natural killer (NK) lymphomas express EBNA-1 and the latent membrane proteins (LMP1-2; type II latency). In contrast to type III EBV-transformed lymphoblastoid cell lines, in these cells the LMPs are expressed in the absence of EBNA-2. We have previously reported that exposure to CD40 ligand and IL-4 could induce LMP-1 in an in vitro EBV-infected Hodgkin lymphoma-derived cell line, which expressed only EBNA-1. We show now that both human and EBV-encoded IL-10 can induce LMP-1 in the absence of EBNA-2 in the Daudi, P3HR1, and other BL cell lines. Interestingly, induction of LMP-1 was not accompanied by the downregulation of BCL-6. IL-10 could also induce LMP-1 in the conditional lymphoblastoid cell line ER/EB2-5 where EBNA-2 was downregulated in the absence of estrogen. Moreover, IL-10 could induce the expression of LMP-1 in tonsillar B cells infected with the nontransforming, EBNA-2-deficient EBV strain P3HR1 and enhance LMP-1 expression in 2 EBV-positive NK lymphoma lines. The demonstration that IL-10 can induce the expression of LMP-1 in an EBNA-2-independent manner shows that the major transforming EBV gene LMP-1 can be induced by extracellular signals in lymphoid cells, and IL-10 might contribute to the establishment of type II EBV latency.
Kis
Lorand L
LL
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden. kis.lorand.levente@mtc.ki.se
Takahara
Miki
M
Nagy
Noemi
N
Klein
George
G
Klein
Eva
E
D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002051:Burkitt Lymphoma / Q000276:immunology*; D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology*; D018123:Receptors, Interleukin / Q000235:genetics; D053701:Receptors, Interleukin-10; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000187:drug effects / Q000235:genetics*; D014764:Viral Proteins
C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D016753:Interleukin-10