Cell‐free Entry of Human T‐Cell Leukemia Virus Type 1 to Mouse Cells

Feng, Renqing; Kabayama, Ayako; Uchida, Keiji; Hoshino, Hiroo; Misawa, Miwa

doi:10.1111/j.1349-7006.2001.tb01110.x

Cited by 9 publications

(8 citation statements)

References 39 publications

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“…However, rats and mice are more attractive models for HTLV-1 study because of the ease with which they can be genetically manipulated. HTLV-1 transmission to newborn mice has been reported and the HTLV-1 provirus in mouse spleen has been detected [21]. Nevertheless, no viral expression or antibody production was detected in these mice and, furthermore, mouse cells seem to be less susceptible to HTLV-1 envelope fusion [22,23], even though some conflicting results have been reported [24].…”

Section: Introductionmentioning

confidence: 99%

CRM1, an RNA transporter, is a major species-specific restriction factor of human T cell leukemia virus type 1 (HTLV-1) in rat cells

Zhang

Hakata

Tanaka

et al. 2006

Microbes and Infection

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Rat ortholog of human CRM1 has been found to be responsible for the poor activity of viral Rex protein, which is essential for RNA export of human T cell leukemia virus type 1 (HTLV-1). Here, we examined species-specific barrier of HTLV-1 by establishing rat cell lines, including both adherent and CD4 + T cells, which express human CRM1 at physiological levels. We demonstrated that expression of human CRM1 in rat cells is not harmful to cell growth and is sufficient to restore the synthesis of the viral structural proteins, Gag and Env, at levels similar to those in human cells. Gag precursor proteins were efficiently processed to the mature forms in rat cells and released into the culture medium as sedimentable viralparticles. An HTLV-1 pseudovirus infection system suggested that the released virus particles are fully infectious. Our newly developed reporter cell system revealed that Env proteins produced in rat cells are fully fusogenic, which is the basis for cell-cell HTLV-1 infection.Moreover, we show that the early steps in infection, from post-entry uncoating to integration into the host chromosomes, occur efficiently in rat cells. These results, in conjunction with reports describing efficient entry of HTLV-1 into rat cells, may indicate that HTLV-1 is unique in that its major species-specific barrier is determined by CRM1 at a viral RNA export step.These observations will enable us to construct a transgenic rat model expressing human CRM1 that is sensitive to HTLV-1 infection.

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Section: Introductionmentioning

confidence: 99%

CRM1, an RNA transporter, is a major species-specific restriction factor of human T cell leukemia virus type 1 (HTLV-1) in rat cells

Zhang

Hakata

Tanaka

et al. 2006

Microbes and Infection

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show abstract

“…The virus consistently infects rabbits (Akagi et al, 1985;Lairmore et al, 1992), some non-human primates (Nakamura et al, 1987;Murata et al, 1996), and to a lesser extent rats (Suga et al, 1991;Ibrahim et al, 1994). Viral transmission in mice using typical methods of infection produces inconsistent infections and limited virus expression in tissues (Fang et al, 1998;Feng et al, 2001;Furuta et al, 2002a, b;Nitta et al, 2003). Nonhuman primates have been infected with HTLV-1 and certain species have a natural infection with simian T-lymphotropic virus infection type 1 (STLV-1) (Gessain and Dethe 1996;Takemura et al, 2002;Gabet et al, 2003).…”

Section: Introductionmentioning

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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“…However, although HTLV-1 consistently infects rabbits [2,3], some non-human primates [4,5], and to a lesser extent, rats [6,7], the virus does not efficiently infect murine cells. Previous studies have indicated that viral transmission in mice, using typical methods of infection, results in inconsistent infections and limited virus expression in tissues [8][9][10].…”

Section: Resultsmentioning

confidence: 99%

The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/¿cnull (NOG) mice

et al. 2014

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Background: Human T-cell leukemia virus type 1 (HTLV-1) causes both neoplastic and inflammatory diseases, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Because these life-threatening and disabling diseases are not yet curable, it is important to prevent new HTLV-1 infections.Findings: In this study, we have established a simple humanized mouse model of HTLV-1 infection for evaluating prophylactic and therapeutic interventions. In this model, HTLV-1-negative normal human peripheral blood mononuclear cells (PBMCs) are transplanted directly into the spleens of severely immunodeficient NOD-SCID/γcnull (NOG) mice, together with mitomycin-treated HTLV-1-producing T cells. Using this model, we tested the efficacy of monoclonal antibodies (mAbs) specific to HTLV-1 as well as human IgG isolated from HAM/TSP patients (HAM-IgG) in preventing HTLV-1-infection. One hour before and 24 h after transplantation of the human cells, each antibody sample was inoculated intraperitoneally. On day 14, human PBMCs isolated from the mouse spleens were tested for HTLV-1 infection. Whereas fresh CD4-positive and CD8-positive T cells isolated from untreated mice or mice treated with isotype control mAb, HTLV-1 non-neutralizing mAbs to envelope gp46, gag p19, and normal human IgG were all infected with HTLV-1; the mice treated with either HTLV-1 neutralizing anti-gp46 mAb or HAM-IgG did not become infected.Conclusions: Our data indicate that the neutralizing function of the antibody, but not the antigen specificity, is essential for preventing the in vivo transmission of HTLV-1. The present animal model will also be useful for the in vivo evaluation of the efficacy of candidate molecules to be used as prophylactic and therapeutic intervention against HTLV-1 infection.

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Cell‐free Entry of Human T‐Cell Leukemia Virus Type 1 to Mouse Cells

Cited by 9 publications

References 39 publications

CRM1, an RNA transporter, is a major species-specific restriction factor of human T cell leukemia virus type 1 (HTLV-1) in rat cells

CRM1, an RNA transporter, is a major species-specific restriction factor of human T cell leukemia virus type 1 (HTLV-1) in rat cells

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

The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/¿cnull (NOG) mice

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