Mouse model for the equilibration interaction between the host immune system and human T-cell leukemia virus type 1 gene expression.
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.
Furuta
Rika A
RA
Department of Microbiology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Sugiura
Kikuya
K
Kawakita
Shigenari
S
Inada
Takefumi
T
Ikehara
Susumu
S
Matsuda
Tadashi
T
Fujisawa
Jun-ichi
J
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D016356:Gene Products, tax / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D020868:Gene Silencing; D049452:Green Fluorescent Proteins; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism / Q000517:prevention & control*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D016356:Gene Products, tax; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins