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11/17. Sequence comparisons of HTLV-I from HAM/TSP patients and their asymptomatic spouses.

    We amplified and sequenced portions of the human T-lymphotropic virus type I (HTLV-I) (U3), pol, env, and pX provirus regions (1212 bp per person) from peripheral blood lymphocytes (PBL) of two married couples (case 1 and case 2). Both husbands are patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and the wives are asymptomatic HTLV-I carriers. We selected these regions because the LTR and env regions of murine retrovirus models have been involved in determining tissue tropism. In addition, the predominant immunogenic epitope for HTLV-I-specific cytotoxic T cells obtained from circulating PBL of HAM/TSP patients was localized in the HTLV-I pX region. Our aim was to examine variations in these HTLV-I regions between affected and asymptomatic spouses. In the HTLV-I regions studied, we detected no sequence variation between each couple. These data do not favor the hypothesis that neurotropic mutants of HTLV-I are involved in the pathogenesis of HAM/TSP.
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keywords = retrovirus
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12/17. sequence analysis of an immunogenic and neutralizing domain of the human T-cell lymphoma/leukemia virus type I gp46 surface membrane protein among various primate T-cell lymphoma/leukemia virus isolates including those from a patient with both HTLV-I-associated myelopathy and adult T-cell leukemia.

    Human T-cell lymphoma/leukemia virus type I (HTLV-I) causes adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy. Specific regions within the outer envelope proteins of other retroviruses, e.g., human immunodeficiency virus type 1, are highly immunogenic and, because of the selective pressure of the host immune system, quite variable. Mutations in the external envelope protein gene of murine retroviruses and human immunodeficiency virus type 1 influence cellular tropism and disease pathogenesis. By contrast, no disease-specific viral mutations have been identified in HTLV-I-infected patients. However, all isolates studied thus far have originated from leukemic cell lines, peripheral blood mononuclear cells, or cerebrospinal fluid lymphocytes from patients with HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma and, therefore, may not truly reflect tissue-associated variation. The midregion of the HTLV-I gp46 external envelope glycoprotein (amino acids 190-209) induces an antibody response in 90% of infected individuals, and a hexapeptide in this region (amino acids 191-196) elicits antibodies in rabbits which inhibit syncytia formation and infection of target lymphocytes. Because of the above, we expected the neutralizing domain of the gp46 env gene of HTLV-I to possess disease or organ-associated mutations selected by the infected host's immune system. Hence, we amplified, cloned, and sequenced HTLV-I dna directly from in vivo central nervous system, spleen, and kidney specimens, and a leukemic cell line from a patient (M. J.) with both HTLV-I-associated myelopathy and adult T-cell leukemia/lymphoma to discern the possibility of tissue- and/or disease-specific variants. In addition, we sequenced several HTLV-I isolates from different regions of the world, including papua new guinea, Bellona, and liberia, and compared them to other previously published HTLV-I and related retroviral sequences. The 239-base pair sequence corresponding to amino acids 178 to 256 in gp46 displayed minor tissue-specific variation in clones derived from central nervous system tissues from patient M. J., but overall was highly conserved at both the dna and amino acid levels. Variation was observed in this region among the other HTLV-I, simian T-cell lymphoma virus type I, and HTLV-II isolates in a pattern that was consistent with their known phylogenetic relationship. No consistent disease-related changes were observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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keywords = retrovirus
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13/17. Tropical spastic paraparesis in an aborigine.

    OBJECTIVE: To present the first documented case of human T-lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis in the Australian population. CLINICAL FEATURES: A 31-year-old Aboriginal man with an 18-month history of progressive weakness of the legs was found to have an upper motor neurone weakness of all limbs associated with sphincteric disturbance and impotence. htlv-i antibodies were detected in his serum and no other cause for the patient's myelopathy could be found. INTERVENTION AND OUTCOME: He was counselled regarding HTLV-I associated myelopathy/tropical spastic paraparesis. CONCLUSION: This is the first description of HTLV-I associated myelopathy/tropical spastic paraparesis in an Australian. In cases of spinal cord disorder without evidence of compression we recommend serological testing for HTLV-I, especially in Aboriginal patients. Additionally, testing of blood donors for this retrovirus needs consideration.
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keywords = retrovirus
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14/17. Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis.

    An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I--associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I--associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were detected in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of this virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.
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keywords = retrovirus
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15/17. HTLV-I associated myelopathy in Porto Alegre (Southern brazil).

    HTLV-I associated myelopathy/tropical spastic paraparesis (TSP/HAM) have been increasingly described in practically all regions of brazil. Five confirmed and documented cases of patients with TSP/HAM in Rio Grande do Sul are reported; in all of them spastic paraparesis, neurogenic bladder and superficial and/or profound sensitive disorders were observed in variable degrees. One patient presented a relapsing-remitting course with a cerebellar ataxia (multiple sclerosis-like pattern). Everyone was submitted to clinical, serological, urodynamic, neurophysiologic and neuroradiologic investigation. The aim of this study was to present the southern region of brazil as an area with significant endemicity for HTLV-I/II infection (prevalence of 0.42% between blood donors), and also to show the existence of patients with neurologic disease associated with this retrovirus.
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keywords = retrovirus
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16/17. Cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein s deficiency in a patient with HTLV-I.

    The clinical spectrum of retroviruses is expanding rapidly. Human T-cell lymphotropic virus type I (HTLV-I) was the first retrovirus to be described, and its role had been established in adult T-cell leukemia/lymphoma and tropical spastic paraparesis. We report the case of a 35-year-old woman with HTLV-I and the unusual combination of cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein s deficiency. We discuss the relationship of all her diseases to HTLV-I.
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ranking = 2
keywords = retrovirus
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17/17. Human T-cell lymphotropic virus type 1 myositis, peripheral neuropathy, and cerebral white matter lesions in the absence of spastic paraparesis.

    BACKGROUND: The human T-cell lymphotropic virus type 1 (HTLV-1) is associated with a chronic, progressive myelopathy termed tropical spastic paraparesis or HTLV-1-associate myelopathy. An increasing number of reports suggest that the spectrum of neurologic diseases associated with HTLV-1 is quite diverse. DESIGN: Case study. SETTING: A university teaching hospital (Ottawa General Hospital, Ottawa, ontario). RESULTS: serum creatine kinase levels were elevated (1091 U/L). Antibodies for HTLV-1 were detected by Western blot analysis and confirmed by polymerase chain reaction. Human immunodeficiency virus antibodies were not detected. Findings of nerve conduction studies revealed an axonal neuropathy, while results of needle electromyography were consistent with mixed neuropathic and myopathic changes. Findings of a muscle biopsy supported the presence of polymyositis. magnetic resonance imaging scans of the brain showed chronic, extensive cerebral white matter involvement of more than 7 years' duration. Treatment with oral steroids resulted in an approximate 40% decrease in serum creatine kinase levels within 1 month and a marked improvement in strength. CONCLUSIONS: A broad spectrum of neurologic disorders is associated with HTLV-1, which may or may not include spastic paraparesis. patients with myopathies and/or neuropathies of unknown origin who are from areas endemic for HTLV-1 should be screened for this retrovirus, even in the absence of spastic paraparesis.
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ranking = 1
keywords = retrovirus
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