HTLV-I Associated Myelopathy, a New Clinical Entity

Osame, Mitsuhiro; Usuku, Koichiro; Izumo, Shuji; Ijichi, Nobuhiro; Amitani, Hiroyoko; Igata, Akihiro; Matsumoto, Makoto; Tara, Mitsutoshi

doi:10.1016/s0140-6736(86)91298-5

Cited by 2,114 publications

(1,107 citation statements)

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“…However, the clinical manifestations of these two viruses differ significantly. HTLV-1 preferentially targets and transforms CD4+ T-cells and is the etiologic agent of adult T-cell leukemia (ATL) (Yoshida et al, 1982) and HTLV associated myelopathy/tropical spastic paraparesis (HAM/TSP) (Osame et al, 1986). HTLV-2 is much less pathogenic, but has been associated with a few cases of atypical hairy cell leukemia and neurological disease (Hjelle et al, 1992;Kalyanaraman et al, 1982).…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…A similar neurological condition was described soon after in Japan and was named HTLV-I-associated myelopathy (HAM). 3 In 1988, both were recognized as being the same disease. The term HTLV-Iassociated myelopathy/tropical spastic paraparesis (HAM/TSP) has been adopted ever since.…”

Section: Introductionmentioning

confidence: 99%

Disability and determinants of gait performance in tropical spastic paraparesis/HTLV-I associated myelopathy (HAM/TSP)

Franzoi

Araújo

2006

Spinal Cord

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Study design: Cross-sectional. Objectives: The aim of this survey is to describe the disability profile in a group of tropical spastic paraparesis/HTLV-I-associated myelopathy patients, identifying the requirements for community ambulation. Setting: Terciary care unit, Rio de Janeiro, Brazil. Methods: Seventy-two patients were assessed (49 female and 23 male), referred by tertiary care centers, when a clinical protocol was applied. Results: The sample had an average age of 40 years and an average of 137 months of duration of the disease. The most prevalent aspects of disability found were in gait and sphincter control areas. A total of 72% of the patients were community ambulators and 17% were restricted to wheel chair. Age, strength and low-back pain interfere in activities of daily living (Po0.05). A positive correlation was found between community ambulation and the knee extensors (r ¼ 0.80) and ankle plantar flexors (r ¼ 0.74). Strength, age, low-back pain, duration of disease, asymmetric onset of the symptoms and spasticity interfered in the ability to walk (Po0.05). A rehabilitation program was proposed focusing on modifiable factors that affect disability level. Conclusion: It was possible to describe the profile of disability in this group of patients, identifying the requirements to the community ambulation. Sponsorship: Not applicable.Spinal Cord (2007) 45, 64-68.

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“…Human T-cell leukaemic virus type 1 (HTLV-1) is a retro-, irus trophic for CD4 + T-cells associated with an aggressive lorm of leukaemia, adult T-cell leukaemia [1,2], and with a ~eurological disorder, tropical spastic paraparesis, also due to infection of T-cells [3]. In order to co-ordinate the regulation ,,f the structural and viral proteins necessary for viral replication a nuclear protein, Rex, encoded in the viral genome, makes efficient use of variably spliced reading frames in the , iral genome (reviewed in [4]).…”

Section: ! Introductionmentioning

confidence: 99%

Enhancement of nucleocytoplasmic export of HTLV‐1 Rex mRNA through cis and trans interactions of the mRNA with the complex of Rex protein and Rex‐responsive element

White

1996

FEBS Letters

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p27 rex of HTLV-1 promotes nucleocytoplasmic t xport of viral mRNAs through binding of the Rex-response element (RexRE) present at the 3' end of the viral transcripts in ds with respect to the ORFs of the viral mRNAs. We have found that expression of the RexRE in trans, as a separate RNA, still allows Rex protein to promote export of viral mRNAs lacking the RexRE. The data suggest the formation of a ternary complex between Rex protein, RexRE and upstream elements of viral mRNA and hence the existence of secondary sites of interaction between Rex protein and viral RNAs.~ey words: mRNA export; HTLV-1; Retrovirus; p27rex; t,'~ex-responsive element; Fluorescence in situ hybridisation !. IntroductionHuman T-cell leukaemic virus type 1 (HTLV-1) is a retro-, irus trophic for CD4 + T-cells associated with an aggressive lorm of leukaemia, adult T-cell leukaemia [1,2], and with a ~eurological disorder, tropical spastic paraparesis, also due to infection of T-cells [3]. In order to co-ordinate the regulation ,,f the structural and viral proteins necessary for viral replication a nuclear protein, Rex, encoded in the viral genome, makes efficient use of variably spliced reading frames in the , iral genome (reviewed in [4]). In the presence of Rex incom-1,1etely spliced transcripts of viral RNA are expressed in the • ytoplasm, allowing expression of proteins from the unspliced :ag-pol transcript and the singly spliced env transcript. In the ,,bsence of Rex the incompletely spliced transcripts remain .equestered in the nucleus to be degraded or for completion ,,f splicing [5,6]. Completely spliced transcripts encode the ~egulatory proteins of the virus, Tax and Rex [5]. Rex works i~y binding directly to a highly structured element of RNA of ~kbout 250 bases present in the viral transcripts, the Rex-re-, ponsive element (RexRE) [7][8][9]. Details of the mechanism of ~tction of Rex, and its analogue Rev from human immunode-!tciency virus (HIV) type 1, are becoming apparent. Despite ~heir lack of sequence homology both proteins contain two orresponding functional domains. The N-terminal domain is ~ich in basic amino acid residues and serves as a nuclear i ocalisation signal, which also has nucleolar localising capabilty [10]. In addition the same domain is the site for multi-' Corresponding author. Fax: (44) (171) 955-4191. E-mail: k.white@umds.ac.ukIbbreviations. FITC, fluorescein isothiocyanate; HIV, human immunodeficiency virus; HTLV-1, human T-cell leukaemic virus type 1 ; NOS, nucleolar localisation signal; RexRE, Rex-responsive element merisation [11] and for binding to the responsive element on the viral RNA [8,12]. A C-terminal domain encodes a leucinerich effector domain which includes a recently characterised nuclear export signal [13,14]. The combination of nuclear import and export signals accounts for the demonstrated ability of Rev to shuttle between the nucleus and cytoplasm [15,16].Two models have been proposed to account for the retention of unspliced viral mRNAs in the nucleus and for the relief of the ...

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HTLV-I Associated Myelopathy, a New Clinical Entity

Cited by 2,114 publications

References 4 publications

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

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

Disability and determinants of gait performance in tropical spastic paraparesis/HTLV-I associated myelopathy (HAM/TSP)

Enhancement of nucleocytoplasmic export of HTLV‐1 Rex mRNA through cis and trans interactions of the mRNA with the complex of Rex protein and Rex‐responsive element

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