Construction and Characterization of Infectious Human T-Cell Leukemia Virus Type 1 Molecular Clones

Kimata, Jason T.; Wong, Fen Hwa; Wang, Jaang J.; Ratner, Lee

doi:10.1006/viro.1994.1581

Cited by 118 publications

(116 citation statements)

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“…Although these types of studies have been very informative, the understanding of HTLV biology and pathogenesis has benefited further from the isolation and manipulation of proviral clones capable of generating infectious virus, and the development and refinement of methodologies for characterization of these clones in primary human T lymphocytes and relevant animal models. It is important to note that HTLV gene structure function studies in the context of a replicating virus were first performed in HTLV-2 due to the availability of an HTLV-2 infectious molecular clone (Chen et al, 1983) over a decade prior to HTLV-1 (Kimata et al, 1994;Derse et al, 1995).…”

Section: Htlv Experimental Systemmentioning

confidence: 99%

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

2005

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Section: Htlv Experimental Systemmentioning

confidence: 99%

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

2005

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“…Four alternative splice acceptor sites at positions 6383, 6478, 6875, and 6950 are utilized to generate the 3′ exon of singly and doubly spliced mRNAs. All HTLV-1 mRNA nucleotide positions above can be converted to ACH provirus (Kimata et al, 1994) numbering by adding 351. Primers across splice junctions and specific probes were designed and utilized to detect and quantify closely related mRNA species.…”

Section: Htlv-1 and Htlv-2 Mrnasmentioning

confidence: 99%

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

Green

2007

Journal of Virological Methods

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SummaryHTLV-1 and HTLV-2 are highly related delta-retroviruses that infect and transform T-lymphocytes, but have distinct pathogenic properties. HTLV replication and survival requires the expression of multiple gene products from an unspliced and a series of highly related alternatively spliced mRNA species. To date, the comparative levels of all known HTLV-1 and HTLV-2 viral mRNAs in different transformed cell lines and at different stages of virus infection have not been assessed. In this study, we compiled a series of oligonucleotide primer pairs and probes to quantify both HTLV-1 and HTLV-2 mRNA species using real-time RT-PCR. The optimized reaction for detection of each mRNA had amplification efficiency greater than 90% with a linear range spanning 25 to 2.5 × 10 7 copies. The R 2 s of all standard curves were greater than 0.97. Quantitation of HTLV mRNAs between different cell lines showed variability (gag/pol ≥ tax/rex > env ≥ accessory proteins), but the overall levels of each mRNA relative to each other within a cell line were similar. These results provide a method to quantify all specific mRNAs from both HTLV-1 and HTLV-2, which can be used to evaluate further viral gene expression and correlate transcript levels to key stages of the virus life cycle and ultimately, pathogenesis.

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“…Infectious molecular clones of HTLV-1 were first developed in the mid-1990s (Kimata et al, 1994;Derse et al, 1995;Zhao et al, 1995). These molecular clones were used to immortalize human PBMCs to create the ACH cell line, which was then used to infect rabbits (Collins et al, 1996).…”

Section: Rabbit 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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Construction and Characterization of Infectious Human T-Cell Leukemia Virus Type 1 Molecular Clones

Cited by 118 publications

References 0 publications

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

Detection and quantitation of HTLV-1 and HTLV-2 mRNA species by real-time RT-PCR

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

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