HTLV‐1‐associated Myelopathy/Tropical Spastic Paraparesis‐like Rats by Intravenous Injection of HTLV‐1‐producing Rabbit or Human T‐Cell Line into Adult WKA Rats

Kushida, Shigeki; Matsumura, Masaru; Tanaka, Hiroko; Ami, Yoshihiro; Hori, Mitsuo; Kobayashi, Mikirou; Uchida, Keiji; Yagami, Ken‐ichi; Kameyama, T; Yoshizawa, Toshihiro; Mizusawa, Hidehiro; Iwasaki, Yuzo; Misawa, Miwa

doi:10.1111/j.1349-7006.1993.tb02052.x

Cited by 18 publications

(14 citation statements)

References 18 publications

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“…Freezing is a state of maintained contracted posture and the decrease of resting/sleeping is possibly a symptom of distress in this pathological condition. These motor abnormalities occurred after 15 months, as also shown by Minagawa et al (3), Ohya (12) and Miyatake et al (13), and with a peak after longer periods, such as 20 months, as shown by our results (2,4,5). The period after 7 months has been pointed out as crucial for molecular events occurring in HAM rats (4,14,15).…”

Section: Discussionsupporting

confidence: 87%

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Motor behavioral abnormalities and histopathological findings of Wistar rats inoculated with HTLV-1-infected MT2 cells

Câmara

Oriá

Felismino

et al. 2010

Braz J Med Biol Res

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Section: Discussionsupporting

confidence: 87%

“…Although lymphocyte infiltration was demonstrated in some rats, this finding was not observed universally, as also reported by others (4,5). In addition, the hematological results were also nonspecific.…”

Section: Discussionmentioning

confidence: 44%

Motor behavioral abnormalities and histopathological findings of Wistar rats inoculated with HTLV-1-infected MT2 cells

Câmara

Oriá

Felismino

et al. 2010

Braz J Med Biol Res

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“…Wistar-King-AptekmanHokudai (WKAH) rats emerged as a model of HAM/ TSP. HTLV-1-infected WKAH rats develop spastic paraparesis with degenerative thoracic spinal cord and peripheral nerve lesions several months following inoculation (Ishiguro et al, 1992;Kushida et al, 1993). The pathology of rat HAM/TSP differs from that seen in humans.…”

Section: Rat Modelsmentioning

confidence: 99%

“…Although initial experimental infection was achieved with F344 rats, it was later established that there was considerable differences in the response of various rat strains to HTLV-1 infection (Ishiguro et al, 1992;Kushida et al, 1993;Ibrahim et al, 1994). Wistar-King-AptekmanHokudai (WKAH) rats emerged as a model of HAM/ TSP.…”

Section: Rat Modelsmentioning

confidence: 99%

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

2005

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Over the past 25 years, animal models of human T-lymphotropic virus type 1 (HTLV-1) infection and transformation have provided critical knowledge about viral and host factors in adult T-cell leukemia/lymphoma (ATL). The virus consistently infects rabbits, some non-human primates, and to a lesser extent rats. In addition to providing fundamental concepts in viral transmission and immune responses against HTLV-1 infection, these models have provided new information about the role of viral proteins in carcinogenesis. Mice and rats, in particular immunodeficient strains, are useful models to assess immunologic parameters mediating tumor outgrowth and therapeutic invention strategies against lymphoma. Genetically altered mice including both transgenic and knockout mice offer important models to test the role of specific viral and host genes in the development of HTLV-1-associated lymphoma. Novel approaches in genetic manipulation of both HTLV-1 and animal models are available to address the complex questions that remain about viral-mediated mechanisms of cell transformation and disease. Current progress in the understanding of the molecular events of HTLV-1 infection and transformation suggests that answers to these questions are approachable using animal models of HTLV-1-associated lymphoma Oncogene (2005) 24, 6005-6015.

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“…For analysis of events in such a latent period, it is necessary to establish an animal model in which the growth of HTLV-1-infected lymphocytes and the host immune system reach a certain balance in vivo. Since HTLV-1 cannot replicate well in mouse cells, a certain strain of rat (17) and SCID mice (27) only have been used as animal models of HTLV-1-related diseases. Mice, however, have a great advantages as model animals, and normal immune reactivity is required to investigate the onset of HTLV-1-related diseases.…”

mentioning

confidence: 99%

Mouse Model for the Equilibration Interaction between the Host Immune System and Human T-Cell Leukemia Virus Type 1 Gene Expression

Furuta

Sugiura

Kawakita³

et al. 2002

J Virol

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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 (4,6,7,25,26) as well as induction of cellular genes including those for interleukin-2 (IL-2) and the IL-2 receptor (2,11,18), and the function of Tax is essential for HTLV-1 transformation of human T lymphocytes (5).In addition, Tax protein plays a role as an immunodominant target antigen recognized by HTLV-1 specific cytotoxic T lymphocytes (CTL) in most HTLV-1-infected individuals (14, 22). In HAM/TSP patients, a high virus load in peripheral blood lymphocytes is observed and a Tax-specific CTL response occurs at a high frequency (14), while low CTL activity has been reported for ATL patients (15). Therefore, a balance between Tax expression and Tax-specific CTL responses is thought to be an important determinant of the development of HTLV-1-related diseases (31). There has been controversy over whether Tax-specific CTL causes or prevents HTLV-1-related diseases, or whether a high viral load in the blood in HAM/TSP patients is a result or a cause of CTL. Recently, it was reported that there is a significant negative correlation between the frequency of Tax-specific CTL and the percentage of HTLV-1-infected CD4 ϩ T cells in the peripheral blood of HAM/TSP patients (10). These results seem to be in accord with the view that Tax-specific CTL protect against disease progression.Furthermore, there remains another unanswered question as to the long latency before the onset of HTLV-1-related diseases. It has been suggested that the latent period involves mutations in the genomes of infected lymphocytes, some part of which have been attributed to the function of Tax protein (13,32), and selection by the host immune system. In fact, it was demonstrated recently that the HTLV-1 tax gene in most leukemic cells from ATL patients accumulated various types of mutations leading to viral escape from the host immune system (9). For analysis of events in such a latent period, it is necessary to establish an animal model in which the growth of HTLV-1-infected lymphocytes and the host immune system reach a certain balance in vivo. Since HTLV-1 cannot replicate well in mouse cells, a certain strain of rat (17) and SCID mice (27) only have been used as animal models of HTLV-1-related diseases. Mice, however, have a great advantages as model animals, and normal immune reactivity is required to investigate the onset of HTLV-1-related diseases.To gain insights into the mechanisms underlying the long latency and onset of HTLV-1-related diseases, we established a simple animal model for investigating the interaction between Tax-expressing cells and Tax-specific immune responses involving mice and syngeneic T lymphoma cells expressing Tax. Focusing on Tax and anti-Tax immune responses, we demonstrated that Tax expression under the control of the HTLV-1 long terminal repeat (LTR) was transiently suppressed in vivo, resulting in a kind of equilibrium between Tax-specific immune responses and ...

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HTLV‐1‐associated Myelopathy/Tropical Spastic Paraparesis‐like Rats by Intravenous Injection of HTLV‐1‐producing Rabbit or Human T‐Cell Line into Adult WKA Rats

Cited by 18 publications

References 18 publications

Motor behavioral abnormalities and histopathological findings of Wistar rats inoculated with HTLV-1-infected MT2 cells

Motor behavioral abnormalities and histopathological findings of Wistar rats inoculated with HTLV-1-infected MT2 cells

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

Mouse Model for the Equilibration Interaction between the Host Immune System and Human T-Cell Leukemia Virus Type 1 Gene Expression

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