High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells

Kushida, Shigeki; Mizusawa, Hidehiro; Matsumura, Masaru; Tanaka, Hirotoshi; Ami, Yoshihiro; Hori, Masataka; Yagami, Ken‐ichi; Kameyama, T; Tanaka, Yuetsu; Yoshida, Akira

doi:10.1128/jvi.68.11.7221-7226.1994

Cited by 28 publications

(12 citation statements)

References 48 publications

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“…A small animal model should be useful to study the pathogenesis of HTLV-1-associated diseases, which is not understood. Although rat models of HTLV-1 infection 9) and HAM/ TSP [10][11][12][13] have been reported, a mouse model would be desirable due to the accumulated information on the genetic background of mice and the advances in transgenic technology.…”

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confidence: 99%

Cell‐free Human T‐cell Leukemia Virus Type 1 Binds to, and Efficiently Enters Mouse Cells

Sun

Nitta

Shoda

et al. 2002

Japanese Journal of Cancer Research

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Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia/ lymphoma and other HTLV-1-associated diseases. However, the interaction between HTLV-1 and T cells in the pathogenesis of these diseases is poorly understood. Mouse cells have been reported to be resistant to cell-free HTLV-1 infection. However, we recently reported that HTLV-1 DNA could be observed 24 h after cell-free HTLV-1 infection of mouse cell lines. To understand HTLV-1 replication in these cells in detail, we concentrated the virus produced from c77 feline kidney cell line and established an efficient infection system. The amounts of adsorption of HTLV-1 are larger in mouse T cell lines, EL4 and RLm1, than those in human T cell lines, Molt4 and HUT78, and are similar to that in human kidney cell line, 293T. Unexpectedly, however, the amounts of entry of HTLV-1 are about 10-fold larger in the two mouse cell lines than those in the three human cell lines employed. Moreover, viral DNA was detectable from 1 h in EL4 and RLm1 cells, but only from 2-3 h in 293T, Molt4 and HUT78 cells. However, the amount of viral DNA in EL4 cells became smaller than that in Molt4 cells. HTLV-1 expression could be detected until day 1-2 in RLm1 and EL4 cells, and until day 4 in Molt4 cells. Our results suggest that mouse cell experiments would give useful information to dissect the early steps of cell-free HTLV-1 infection.Key words: Cell-free HTLV-1 -Entry -Expression -Mouse cells Human T-cell leukemia virus type 1 (HTLV-1) is believed to be a causative agent of adult T-cell leukemia/ lymphoma (ATL), 1, 2) HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), [3][4][5] and other HTLV-1-associated diseases.6, 7) Among infected individuals, only 2 to 3% develop ATL.8) In addition, there is a latency of 40 to 50 years before manifestation of ATL. A small animal model should be useful to study the pathogenesis of HTLV-1-associated diseases, which is not understood. Although rat models of HTLV-1 infection 9) and HAM/ TSP 10-13) have been reported, a mouse model would be desirable due to the accumulated information on the genetic background of mice and the advances in transgenic technology.Recently, we reported HTLV-1 transmission to newborn mice [14][15][16] by inoculating them with an HTLV-1-producing human T cell line, MT-2.17) In addition, although it was reported that mouse cell lines are very resistant to cell-free HTLV-1 infection, 18) we have recently found that cell-free HTLV-1 can enter many mouse cell lines. 19)The kinetics of HTLV-1 replication is not well understood, mainly due to the unavailability of efficient cell-free HTLV-1 infection. Although Fan et al. developed a sensitive HTLV-1 infection assay with cell-free HTLV-1 produced from MT-2 cells, only low levels of viral DNA have been detected. 20) Haraguchi et al. reported that the cell-free HTLV-1 produced from a feline kidney cell line, c77, is highly transmissible to human cells. The transmission of cell-free HTLV-1 produced from c77 cells was estimated to...

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mentioning

confidence: 99%

Cell‐free Human T‐cell Leukemia Virus Type 1 Binds to, and Efficiently Enters Mouse Cells

Sun

Nitta

Shoda

et al. 2002

Japanese Journal of Cancer Research

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“…In in vitro experiments, it was shown that HTLV-1 is able to infect a variety of cell lines, including B cells, endothelial cells, glial cells and fibroblasts. [5][6][7][8] Monkeys, rabbits and rats, besides humans, are susceptible to HTLV-1 infection, [9][10][11] but it was reported that the plating efficiency of vesicular stomatitis virus pseudotype bearing HTLV-1 envelope glycoprotein on mouse cells was approximately 1% of that on human cells. 12) There has been little work on experimental HTLV-1 infection in mouse.…”

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confidence: 99%

Human T‐cell Leukemia Virus Type 1 Can Infect a Wide Variety of Cells in Mice

Feng

Tanaka

Abe

et al. 1999

Japanese Journal of Cancer Research

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“…Using these susceptible animals, several animal models have been developed to study HTLV-1-associated diseases. The HAM/TSP-like disease model in rats of the WKA strain is well established and has been used to dissect the pathogenic mechanisms of the disease (14,23). On the other hand, a few ATL model systems have been established so far by using rabbits and rats, but their utility is limited.…”

mentioning

confidence: 99%

Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells

Ohashi

Hanabuchi

Kato

et al. 1999

J Virol

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Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic to nu/nurats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in newborn nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newbornnu/nu rats acquired the potency to grow in adultnu/nu rats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection.

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High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells

Cited by 28 publications

References 48 publications

Cell‐free Human T‐cell Leukemia Virus Type 1 Binds to, and Efficiently Enters Mouse Cells

Cell‐free Human T‐cell Leukemia Virus Type 1 Binds to, and Efficiently Enters Mouse Cells

Human T‐cell Leukemia Virus Type 1 Can Infect a Wide Variety of Cells in Mice

Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells

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