Influence of Epstein–Barr virus infection in adult T-cell leukemia

Abstract

The involvement of adult T-cell leukemia (ATL) cells in organs such as the skin and lymph nodes is observed in about 50% of cases of ATL. Epstein-Barr virus (EBV) infection has often been observed in the clinical course of ATL. In this study, we established two B-cell lines from peripheral blood of patients with ATL. EBV DNA, proviral DNA for HTLV-1 and Tax mRNA were detected in both lines. As part of the characterization of these cells, an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) (CD54) or ICAM-3 (ICAM-3) (CD50), lymphocyte function-1 (LFA-1) (CD11a/CD18), and Mac-1 (CD11b/CD18) was observed. To investigate the role of the interaction of these viruses, we transfected EBV and/or HTLV-1 into a healthy donor's lymphocytes, an EBV-infected B cell line, Raji, and a HTLV-1 negative T-cell line, Jurkat. Enhanced expression of adhesion molecules was also observed in double transfectants (EBV and HTLV-1). In the clinical course of ATL, LMP-1, EBNA-2, CD50 and CD54 were detected in lymph nodes and skin specimens by immunohistochemical staining. Furthermore, high levels of interleukin-4 (IL-4) were detected in these cell lines and transfectants. The results indicated that coinfection with HTLV-1 and EBV may induce aggressive organ involvement through the enhanced expression of adhesion molecules via IL-4 signaling. A new mechanism of ATL involvement is discussed.

Quantitative Comparison of HTLV-1 and HIV-1 Cell-to-Cell Infection with New Replication Dependent Vectors

“…In addition to the high levels Luc transduction, we chose to use Raji/CD4 cells in the following experiments for several reasons. First, B-cells are natural targets for HTLV-1 infection in vivo and in vitro [35],[36],[37],[38],[39]. Furthermore, B-cells were shown to form conjugates (virological synapses) with HTLV-1-infected T cells in PBMC cultures from HTLV-1-infected individuals [14].…”

“…We are currently examining these possibilities. Although Raji/CD4 cells are not natural targets for HIV-1 infection, we believe that they do provide an appropriate model system to study HTLV-1 cell-to-cell infection, as B-cells are natural targets for HTLV-1 infection in vivo and in vitro [35],[36],[37],[38],[39] and can form synapses with HTLV-1-infected T lymphocytes in vitro [14]. While it is desirable to examine cell-to-cell infection using primary T-cells as targets, we have been unable to detect Luc transduction in cocultures of transfected Jurkat T-cells and activated CD4 + T-cells.…”

Adult T-cell leukemia/lymphoma with Epstein-Barr virus–positive Hodgkin-like cells

“…CD21 is the EBV-receptor and is reported to be over expressed in CD4+ T cells in ATLL as a result of the stimulatory influence of the HTLV-1 Tax protein; however, evidence of EBV DNA integration could not be demonstrated in these cells, questioning the role of EBV in the ATLL leukemogenesis [11]. In contrast, a recent study purports that coinfection with HTLV-1 and EBV may be associated with a greater likelihood of organ involvement and a more aggressive course through the enhanced expression of adhesion molecules via increased IL-4 signaling [12]. …”

“…[11, 12]. Plausibly patients with ATLL may be more susceptible to this infection than patients with other types of lymphoma due to the levels of immunosuppression [1].…”

Diffuse Large B-Cell Lymphoma in Human T-Lymphotropic Virus Type 1 Carriers

“…In a previous paper in patients with ATLL, Ueda et al indicated that coinfection with HTLV-1 and EBV may induce a more extensive organ involvement through the enhanced expression of adhesion molecules via IL-4 signaling [21]. Similarly, Ogata et al found a subclinical reactivation of EBV in ATLL patients undergoing chemotherapy [22].…”