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Journal of Virology, March 2002, p. 2703-2713, Vol. 76, No. 6
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.6.2703-2713.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Department of Microbiology,1 First Department of Pathology,3 Department of Urology,4 Department of Anesthesiology,5 Transplantation Center, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan2
Received 11 July 2001/ Accepted 17 December 2001
To study the involvement of immune responses against Tax of human T-cell leukemia virus type 1 (HTLV-1) in the growth of and gene suppression in Tax-expressing tumor cells in vivo, we established a model system involving C57BL/6J mice and a syngeneic lymphoma cell line, EL4. When mice were immunized by DNA-based immunization with Tax expression plasmids, solid tumor formation upon subcutaneous inoculation of EL4 cells expressing green fluorescent protein-fused Tax (Gax) under the control of the HTLV-1 enhancer was strongly inhibited, and in vitro analysis showed that DNA immunization elicited cytotoxic T-lymphocyte (CTL) responses but not production of antibodies to Tax protein. Since EL4/Gax cells inoculated into DNA-immunized mice were not completely eradicated but were maintained as small solid tumors for a long period, there appeared to be a certain equilibrium between CTL activity and the growth of Gax-expressing cells. With such a balance, expression of the Gax gene in EL4/Gax cells was strongly suppressed. These results suggested that gene expression under the control of the HTLV-1 long terminal repeat and Tax is silenced in vivo, resulting in an equilibrium between viral expression and the host immune system. Such a balance would represent a status of persistent infection by HTLV-1 in virus-infected individuals during the latency period.
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