Establishment of a seronegative human T-cell leukemia virus type 1 (HTLV-1) carrier state in rats inoculated with a syngeneic HTLV-1-immortalized T-cell line preferentially expressing Tax.
Human T-cell leukemia virus type 1 (HTLV-1) causes T-cell malignancies in a small percentage of the population infected with the virus after a long carrier state. In the present study, we established a seronegative HTLV-1 carrier state in rats inoculated with a newly established HTLV-1-infected rat T cell line, FPM1. FPM1 originated from rat thymocytes cocultured with a human HTLV-1 producer, MT-2 cells, and expressed rat CD4, CD5, CD25, and HTLV-1 Tax. However, FPM1 scarcely expressed other major HTLV-1 structural proteins and failed to induce typical antibody responses against HTLV-1 in inoculated rats. In contrast, control rats inoculated with MT-2 cells generated significant levels of anti-HTLV-1 antibodies. HTLV-1 proviruses were detected in peripheral blood cells of syngeneic rats inoculated with FPM1 for more than 1 year. Analysis of the flanking region of HTLV-1 provirus integrated into host cells suggested that FPM1 cells remained in these animals over a relatively long period of time. However, a similar seronegative HTLV-1 carrier state was induced in the rats inoculated with mitomycin C-treated FPM1 cells and also in FPM1-inoculated allogeneic rats, suggesting that FPM1 could also transmit HTLV-1 into host cells in vivo. Our findings indicated that (i) HTLV-1-immortalized T cells which preferentially express HTLV-1 Tax persisted in vivo but failed to induce any diseases in immunocompetent syngeneic rats and that (ii) suboptimal levels of HTLV-1 for antibody responses allowed the establishment of persistent HTLV-1 infection.
Department of Immunotherapeutics, Tokyo Medical and Dental University, Medical Research Division, Tokyo 113, Japan.
Y
Y
Koya
T
T
Ohashi
H
H
Kato
S
S
Hanabuchi
T
T
Tsukahara
F
F
Takemura
K
K
Etoh
M
M
Matsuoka
M
M
Fujii
M
M
Kannagi
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002353:Carrier State; D002461:Cell Line, Transformed; D015485:Deltaretrovirus Antigens / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015686:Gene Products, env / Q000032:analysis; D015683:Gene Products, gag / Q000032:analysis; D016356:Gene Products, tax / Q000096:biosynthesis; D015490:HTLV-I Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D011533:Proviruses; D012367:RNA, Viral; D051381:Rats; D011916:Rats, Inbred F344; D015682:Retroviridae Proteins, Oncogenic / Q000032:analysis; D016662:Virus Integration; D017735:Virus Latency; D054301:gag Gene Products, Human Immunodeficiency Virus
D000914:Antibodies, Viral; D015485:Deltaretrovirus Antigens; D015686:Gene Products, env; D015683:Gene Products, gag; D016356:Gene Products, tax; D012367:RNA, Viral; D015682:Retroviridae Proteins, Oncogenic; D054301:gag Gene Products, Human Immunodeficiency Virus; C055266:gp46 protein, Human T-cell leukemia virus type I; C060955:p19 protein, Human T-lymphotropic virus 1