HTLV-I DNA Research Articles

Highly sensitive label-free fluorescence determination of lymphotropic virus DNA based on exonuclease assisted target recycling amplification and in-situ generation of fluorescent copper nanoclusters

Specific and sensitive detection of target DNA plays a significant role in clinical diagnosis and biomedical research. Herein, a sensitive ratio fluorescence biosensor was constructed based on in-situ generation of fluorescent copper nanoclusters (CuNCs) on the DNA modified graphene quantum dots (GQDs) for the detection of HTLV-I DNA. Firstly, large amount of AT rich single DNA (o-DNA) can be released from the designed hairpin DNA in the presence of trace target DNA via exonuclease III assisted target recycling amplification strategy. Then, the released o-DNA hybridized with the complementary DNA1 which was modified on the surface of GQDs, and the formed hybridized DNA with blunt 3′-hydroxylated terminus that couldn’t be digested by exonuclease I could act as the template for the generation of fluorescent CuNCs. While in the absence of target DNA, the o-DNA couldn’t be released, thus the DNA1 with 3′overhang ends could be degraded by exonuclease I, which resulted in the in-situ generation of fluorescent CuNCs on the surface of GQDs was blocked owing to the lack of DNA template. The GQD fluorescence in the GQD-CuNC nanohybrid was almost uninfluenced during the whole process. Therefore, with the GQD serving as the reference and CuNC acting as the reporter signal, there was an excellent linear relationship between the change of fluorescence intensity ratio (F595/F445) and the concentration of HTLV-I DNA in the range of 20 pM-12 nM with a detection limit of 10 pM. Furthermore, the biosensor exhibited satisfactory results for monitoring the presence of HTLV-I DNA in human serum.

Comparison of HTLV-I Proviral Load in Adult T Cell Leukemia/Lymphoma (ATL), HTLV-I-Associated Myelopathy (HAM-TSP) and Healthy Carriers.

Human T Lymphocyte Virus Type one (HTLV-I) is a retrovirus that infects about 10-20 million people worldwide. Khorasan province in Iran is an endemic area. The majority of HTLV-I-infected individuals sustain healthy carriers but small proportion of infected population developed two progressive diseases: HAM/TSP and ATL. The proviral load could be a virological marker for disease monitoring, therefore in the present study HTLV-I proviral load has been evaluated in ATL and compared to HAM/TSP and healthy carriers. In this case series study, 47 HTLV-I infected individuals including 13 ATL, 23 HAM/TSP and 11 asymptomatic subjects were studied. Peripheral blood mononuclear cells (PBMCs) were investigated for presence of HTLV-I DNA provirus by PCR using LTR and Tax fragments. Then in infected subjects, HTLV-I proviral load was measured using real time PCR TaqMan method. The average age of patients in ATL was 52±8, in HAM/TSP 45.52±15.17 and in carrier's 38.65±14.9 years which differences were not statistically significant. The analysis of data showed a significant difference in mean WBC among study groups (ATL vs HAM/TSP and carriers P=0.0001). Moreover, mean HTLV-I proviral load was 11967.2 ± 5078, 409 ± 71.3 and 373.6 ± 143.3 in ATL, HAM/TSP and Healthy Carriers, respectively. The highest HTLV-I proviral load was measured in ATL group that had a significant correlation with WBC count (R=0.495, P=0.001). The proviral load variations between study groups was strongly significant (ATL vs carrier P=0.0001; ATL vs HAM/TSP P= 0.0001 and HAM/TSP vs carriers P< 0.05). Conclusion : The present study demonstrated that HTLV-I proviral load was higher in ATL group in comparison with HAM/TSP and healthy carriers. Therefore, HTLV-I proviral load is a prognostic factor for development of HTLV-I associated diseases and can be used as a monitoring marker for the efficiency of therapeutic regime.

Combination Chemotherapy with CHOP-Daclizumab in HTLV-I Associated Adult T-Cell Leukaemia/Lymphoma.

Adult T-cell leukaemia/lymphoma (ATLL) is a lymphoproliferative disorder linked aetiologically to the retrovirus HTLV-I. Despite new insights into the pathogenesis of ATLL, there has been little improvement in the treatment or survival of these patients. Since ATLL express abundant surface IL2-R (CD25), and following from the results with unmodified anti-CD25, we combined daclizumab (Zenapax - Roche) with standard CHOP to assess the feasibility of this combination. Eligibility criteria included: histologically confirmed ATLL requiring treatment, no previous therapy with anthracycline based chemotherapy, age 18–75 and informed consent. CHOP-daclizumab drug schedule: day 1 cyclophosphamide 750mg/m2 iv, doxorubicin 50mg/m2 iv, vincristine 1.4mg/m2 (max 2mg) iv, day 1–5 prednisolone 100mg po, and daclizumab 1mg/kg iv on day 7 and 14 during first cycle, and on day 1 from cycle 2 to 6. Daclizumab was administered on day 7 due to expected high levels of soluble IL2-R which would saturate the antibody activity. Cycles were repeated every 21 days. Infection prophylaxis included co-trimoxazole, itraconazole and acyclovir. Patients had weekly CMV PCR monitoring. Ten patients were enrolled into the study between February 2004 and October 2005 (9 females,1 male, median age 44 years (range 27–61 years). 9 patients were of Caribbean origin and 1 African. Five patients presented with acute leukaemia, four with lymphoma type and one with chronic ATLL. The main disease features were: lymphadenopathy (80%), hypercalcaemia (50%, median serum calcium 3.23 mmol/L), organomegaly (40%), skin lesions (20%), CNS symptoms (10%). Six patients had peripheral blood lymphocytosis (range 10–96x109/l), serum LDH was elevated in 9 patients (380–6065 IU/L, NR <240 IU/L), six patients had LDH level more than 3 times above normal. All patients had serum antibodies to HTLV-I detected by ELISA and Western blot analysis. Median HTLV-I viral load 75.8 HTLV-I DNA copies/100 PBMCs (Leukaemia 100.4 copies/100 PBMCs; Lymphoma 27.8 copies/100 PBMCs). None of our patients received previous treatment for ATLL. Eight patients completed 6 cycles of treatment, one patient 4 cycles and one patient 3 cycles. Treatment was well tolerated and no unexpected toxicities, in particular viral complications, were observed. 50% of patients achieved CR with 2 patients remaining in CR after >24 months of follow up. The other 3 patients suffered early relapse (after 1–3 months) and died from progressive disease. Two patients achieved PR, and 3 had progressive disease while on treatment. Seven out of 10 patients died 4–19 months from the diagnosis. Three patients are alive (2 in CR and 1 in PR - maintained on interferon/tenofovir) with median follow up of 23 months (range 11–30 months).Our data confirm that daclizumab in combination with CHOP chemotherapy is feasible with a response rate of 70%. There is minimal added toxicity, and specifically no added viral infections. However, the short duration of response remains the main problem in ATLL treatment and future studies with increased doses of daclizumab in addition to long term maintenance are warranted.

Proposal for Diagnostic Criteria of Tropical Spastic Paraparesis/HTLV-I-Associated Myelopathy (TSP/HAM)

After the first description of TSP/HAM in 1985 and the elaboration of WHO's diagnostic criteria in 1988, the experience of the professionals in this field has increased so that a critical reappraisal of these diagnostic guidelines was considered timely. Brazilian neurologists and observers from other countries met recently to discuss and propose a modified model for diagnosing TSP/HAM with levels of ascertainment as definite, probable, and possible, according to myelopathic symptoms, serological findings, and/or detection of HTLV-I DNA and exclusion of other disorders.

Evaluation of HTLV-I removal by filtration of blood cell components in a routine setting.

WBC depletion by filtration may prevent the transmission of HTLV-I, which requires cell-to-cell contact. The removal of HTLV-I-infected cells in routinely filtered blood cell components was measured. The study was conducted in Martinique where systematic screening for HTLV-I and -II and universal leukoreduction are mandatory. HTLV-I was quantified by use of real-time PCR in 8 RBC units and 4 PLT concentrates before and after filtration. HTLV-I proviral load in PBMNCs was determined in five of the eight HTLV-I-infected blood donors. The amount of MNC-associated HTLV-I DNA in RBC units before filtration was 21 x 10(6)+/- 29 x 10(6) copies (mean +/- SD). HTLV-I was detected in 4 of 8 RBC units after filtration, with a number of copies in the MNC fraction ranging from 20 to 140, following a 4.9 to 5.8 log reduction. Flow cytometry analysis performed in 2 of the filtered RBC units containing detectable HTLV-I showed suboptimal and out-of-range leukoreduction (0.56 x 10(6) and 1.22 x 10(6) residual WBCs). HTLV was not detected in filtered RBCs from the blood donor with the highest percentage of HTLV-I-infected PBMCs (9%). This study confirms that HTLV-I-infected cells can be detected in filtered blood cell components and shows that optimal leukoreduction is critical for HTLV-I removal.

Real-time polymerase chain reaction assay for cell-associated HTLV type I DNA viral load.

We have developed a quantitative real-time PCR assay for HTLV-I DNA. This assay approach uses real-time monitoring of fluorescent signal generation as a consequence of Taq-mediated amplification of specific target sequences to allow real-time kinetic analysis of amplicon production. This kinetic approach yields excellent sensitivity and an extremely broad linear dynamic range, and ensures that quantitation is based on analysis during the exponential phase of amplification, regardless of the input template copy number. The HTLV-I DNA assay has a nominal threshold sensitivity of 10 copy Eq/reaction, although single-copy plasmid template can be detected at frequencies consistent with statistical prediction. The linear dynamic range is in excess of 5 logs. Interassay reproducibility averages 14% (coefficient of variation) for control templates over a range of 10(1) to 10(6) copy Eq/reaction and 25%, based on studies of extraction and analysis of replicate aliquots of PBMC specimens from HTLV-I-infected subjects. The primer/probe combination targets tax sequences conserved across described HTLV-I and HTLV-II isolates. Parallel quantitation in the same samples of an endogenous sequence present at a known copy number per cell allows normalization of results for potential variation in DNA recovery. Availability of this assay should facilitate studies of basic pathogenesis and clinical evaluation of HTLV-I and HTLV-II infection, as well as assessment of therapeutic approaches.

Leucemia linfoma T del adulto en Chile.: Estudio clínico-patológico y molecular de 26 pacientes

Adult T cell leukemia lymphoma is a lymphoproliferative syndrome etiologically associated to human T cell lymphotropic virus type I. To describe the clinical and laboratory features of 26 Caucasian Chilean patients, with HTLV-I positive adult T-cell leukemia lymphoma (ATLL). Diagnostic criteria included clinical features, cell morphology, immunophenotype, HTLV-I serology and/or DNA analysis by Southern blot or PCR. According to the clinical presentation, 12 cases had the acute ATLL form, 6 had a lymphoma, 4 the chronic form and 4 had smoldering ATLL. The median presentation age was 50 years, younger than the Japanese patients, but significantly older than patients from other South American countries (e.g. Brasil, Jamaica, Colombia). The main clinical features: lymphadenopathy, skin lesions and hepatosplenomegaly, were similar in frequency to those of patients from other countries, except for the high incidence of associated neurological disease. Tropical Spastic Paraparesis (TSP) in our series of ATLL, was seen in one third of the patients (8/26). A T-cell immunophenotype was shown in all 26 cases and HTLV-I serology was positive in 25/26 patients. Molecular analysis on the seronegative patient showed clonal integration of proviral HTLV-I DNA into the lymphocytes DNA, and thus he may have been a poor responder to the retroviral infection. Proviral DNA integration was also demonstrated in 15/16 patients being clonal in 10, polyclonal in 3 (all smoldering cases) and oligoclonal in one. ATLL in Chile has similar clinical and laboratory features than the disease in other parts of the world, except for a younger age than Japanese patients but older than those from other Latin American countries and a high incidence of patients with associated TSP. Detailed morphological and immunophenotypic analysis of the abnormal circulating lymphocytes, together with the documentation of HTLV-I by serology and/or DNA analysis are key tests for the identification of this disease.

Human Complement Component C1q Inhibits the Infectivity of Cell-Free HTLV-I

Human T cell leukemia virus type I (HTLV-I) is a retrovirus that is not lysed by human serum or complement. It has not been determined, however, whether HTLV-I directly binds to complement components or whether it retains infectivity after incubation with human serum. We investigated the effects of human serum on the infectivity of cell-free HTLV-I produced by human and animal cells. Plating of vesicular stomatitis virus (HTLV-I) pseudotypes prepared in cat or human cells and formation of HTLV-I DNA after infection of cell-free HTLV-I produced by cat or human cells were markedly inhibited by treatment with fresh human serum, but not by heat-inactivated serum. HTLV-I infection was also inhibited by treatment with C2-, C3-, C6-, or C9-deficient serum, but not by C1q-deficient serum. Inhibitory activities of normal human serum against HTLV-I were neutralized by anti-C1q serum. Furthermore, purified C1q inhibited HTLV-I infection. The direct binding of C1q to HTLV-I was confirmed by comigration of C1q with HTLV-I virion upon sucrose density gradient ultracentrifugation of HTLV-I virion treated with C1q. Binding assay using synthetic envelope peptides indicated that C1q bound to an extramembrane region of the gp21 transmembrane protein. These findings indicate that the human complement component C1q inactivates HTLV-I infectivity.

Evidence of HTLV-I in thyroid tissue in an HTLV-I carrier with Hashimoto's thyroiditis.

Human T-lymphotropic virus type l (HTLV-I) protein and messenger RNA (mRNA) for HTLV-I were examined in thyroid tissues from two patients with Hashimoto's thyroiditis and serum anti-thyroid antibody. The virus envelope protein and signals for the mRNA were detected in many of the follicular epithelial cells of the thyroid tissue from one of the patients, respectively, by immunohistochemistry and in situ hybridization. PCR-Southern blotting revealed the presence of HTLV-I DNA in the thyroid tissue, in which the viral protein and mRNA were detected, although no virus particles were found in the epithelial cells by electron microscopy. HTLV-I virus was not present in the thyroid tissue from the second patient. The present findings suggest that infection of thyroid tissue with HTLV-I is associated with the pathogenesis of Hashimoto's thyroiditis in some patients.

Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production.

The immunopathology of human T cell lymphotropic virus type 1 (HTLV-I) uveitis was addressed by using T cell clones (TCC) established from the intraocular fluid of patients with HTLV-I uveitis. Proviral DNA of HTLV-I was identified in 55 out of 94 (59%) or 13 out of 36 (36%) TCC from the ocular fluid or the peripheral blood of these patients, respectively. Most of HTLV-I-infected TCC had a CD3+ CD4+ CD8- phenotype. HTLV-I infection on TCC was confirmed by analysis of the viral mRNA, nucleotide sequence, virus-associated proteins, and virus particles. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1 alpha (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1,268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5,095 pg/ml), and GM-CSF (2,886 pg/ml). Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases. In summary, the results demonstrated direct evidence of HTLV-I infection of the eye and suggest that cytokines produced by HTLV-I-infected T cells are responsible for the intraocular inflammation in patients with HTLV-I uveitis.

Clonality of Benign Lymphoid Hyperplasia in Orbit and Conjunctiva

In order to thoroughly characterize the clonal population of lymphoid hyperplasia of the orbit and conjunctiva, we investigated six cases which were histologically proven to be benign lymphoid hyperplasia. We analyzed the clonal rearrangements of the antigen receptors and bcl-2 gene, Epstein-Barr virus (EBV), and human T-cell leukemia virus type 1 (HTLV-I) by Southern blot and/or polymerase chain reaction (PCR), and performed in situ hybridization for mRNA of kappa and lambda immunoglobulin. Five cases showed rearrangements of immunoglobulin heavy chain gene (JH) and/or light chain gene (J kappa), and the monoclonal V-J recombination of JH in PCR. However, the rearranged bands were much more faint than was the germ-line band. We considered the monoclonal population of B cells small. Two of the five cases recurred locally after four and nine years respectively. Because benign lymphoid hyperplasias frequently contain an occult monoclonal B-cell population, a follow-up should be conducted. The remaining case in our investigation showed a rearrangement of the T-cell-receptor gene and proviral DNA of HTLV-I, and it showed rapid progress to adult T-cell leukemia after the biopsy. EBV and bcl-2 gene rearrangements were not observed in any of the six cases we studied.

ANTI-RETROVIRUS ANTIBODIES IN INSULIN-DEPENDENT DIABETIC CHILDREN AT DIAGNOSIS AND DURING 1–2.6 YRS FOLLOW-UP

Viruses have long been implicated in the pathogenesis of insulin-dependent diabetes (IDDM). Recently it has been observed that β-cell specific expression of endogenous retrovirus is associated with the development of insulins and diabetes in non-obese diabetic (NOD) mice. The aim of our study was to evaluate the presence of retroviral markers in 27 newly diagnosed IDDM children, aged 9.6±3.8 yrs (range 3-15.9 yrs). In all patients anti-islet cell (ICA), anti-insulin (IAA), anti-thyroid (TgA and MsA) antibodies were evaluated and HLA typing was performed. Virological studies included the search for anti-retrovirus (HTLVs) antibodies using the western immunoblotting (WIB) and the HTLV-I DNA amplification by polymerase chain reaction (PCR) for tax/rex pol, and gag (PIS) regions. At onset of IDDM ICA were present in 19 patients (70%) and IAA in 2 of them, while all patients were negative for TgA and MsA. HTLVs antibodies were detected in 10 out of the 27 patients (37%) while no HTLV-I DNA sequencies were detected using our PCR assay. Interestingly, we have observed a frequent association between the presence of HTLVs antibodies and the presence of HLA-DR3 and DQ2 antigens. Until now, during 1-2.6 yrs follow-up we could revalue 13 children, four with HTLVs antibodies and 9 without antibodies. In 2/4 patients the HTLVs antibodies disappeared and in another boy, with five antibodies at onset of IDDM (directed against p 19, rgp21, p24, p26, p36) only one antibody (directed against rgp 21) was constantly present.

Polymerase chain reaction amplified HTLV-I, HIV-1 and HIV-2 DNA fragments in subjects with mixed retroviral infections.

Serum and peripheral blood mononuclear cells from eight patients from the Ivory Coast with positive screening test results for retroviral infections were studied by serology (ELISA, Western blot (WB), synthetic peptide test), cell co-culture, and polymerase chain reaction (PCR). Two HIV-2 infections with indeterminate interpretation on HIV-1 WB were detected, two were clear dual HIV-1/HIV-2 infections, three were ambiguous mixed HIV-1/HIV-2 infections, and one was a triple retroviral infection by HTLV-I, HIV-1 and HIV-2. Four slow/low HIV-1 strains were isolated at the expense of HTLV-I and HIV-2 strains. The ELISA tests were found to be very sensitive. Indeterminate WB interpretations were frequent (HTLV-I, four; HIV-1, three; HIV-2, two). PCR provided clear evidence of multiple retroviral infections in three cases and enabled interpretation of indeterminate WB samples in three cases. One sample presented a puzzling pattern with positive PCR results for HIV-1 and HIV-2 associated with negative or indeterminate serological results. Thus, our data emphasise the need to analyse serological as well as virological markers to gain better insight on mixed retroviral infections, especially in endemic areas such as West Africa.

HTLV-I uveitis in a rabbit

An animal model of HTLV-I associated uveitis was created. One rabbit developed bilateral uveitis 3,5 years after being injected with blood from an HTLV-I-infected rabbit. The proviral DNA of HTLV-I was detected by polymerase chain reaction and dot-blot hybridization in the aqueous humor of the anterior chamber and the vitreous body. Histopathological examination revealed marked corneal opacity with neovascularization and infiltration of inflammatory cells, mainly plasma cells, into the iris, ciliary body, and choroid. Complicated cataracts were also seen. The retinas were destroyed and replaced by gliosis. This is the first animal model of HTLV-I-associated disease to be reported.

Absence of HTLV-I and HTLV-II Proviral Genome in the Brains of Patients with Multiple Sclerosis and Amyotrophic Lateral Sclerosis

Previous studies have failed to provide serological evidence to incriminate a retroviral infection in the cause of multiple sclerosis. Gene amplification techniques have also failed to identify retroviral footprints in DNA from peripheral blood leukocytes. Here we provide evidence that proviral DNA of HTLV-I and HTLV-II is not found in the central nervous system tissues of patients with multiple sclerosis, patients with amyotrophic lateral sclerosis and controls.

No Detection of HTLV-I DNA in Punch Skin Biopsies from Patients with Cutaneous T-Cell Lymphoma by the Polymerase Chain Reaction

In this study we have tried to take advantage of the high genetic homology between conserved regions of human T-cell lymphotropic virus (HTLV) types I and II, hoping that a possible retrovirus in patients with cutaneous T-cell lymphoma (CTCL) would have regions with homology to types I/II. DNA was extracted from punch skin biopsies from 21 patients and subjected to the polymerase chain reaction (PCR), using primer sets designed to match conserved regions in the HTLV-I/II genome. The PCR products were subjected to agarose gel electrophoresis with subsequent Southern blotting and hybridization to an HTLV-I probe. No bands of exogenous origin were seen on the agarose gel or by hybridization. If a retrovirus is present in the skin in CTCL patients, it is either not related to HTLV-I/II, present at a copy number below the PCR detection limit, or has been cleared from the skin before the clinical symptoms appear.

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV‐I endemic area to find out if HTLV‐I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non‐uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20–49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV‐I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV‐I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV‐I causes a specific type of intraocular inflammation, uveitis.

Overt and latent HIV 1 and HTLV-I infection in cohorts of at high risk individuals in Argentina

We conducted a survey using serology and polymerase chain reaction assays to detect HIV 1 and/or HTLV-I antibodies and viral DNA, respectively, in 113 intravenous drug abusers and in 62 sexually active high risk individuals attending two Drug Addict Centres and a Centre for Venereal Diseases in Buenos Aires, Argentina. At the time of the survey 137 of these subjects were known to be HIV 1 seropositive but none of them was symptomatic. Serological tests for HTLV-I were found to be positive in 38 (21.7%) of the HIV 1 positive individuals, whereas all of the 38 HIV 1 seronegative subjects were also seronegative for HTLV-I antibodies. Gene amplification assays carried out in blood sample DNA from the 38 HIV 1/HTLV-I seronegative individuals, revealed HIV 1 DNA in six out of 28 intravenous drug abusers (21.5%). One subject (2.6%) was positive for both HIV 1 and HTLV-I DNA sequences, whereas four (10.5%) showed HTLV-I DNA only. To determine whether these individuals were infected with HTLV-I and/or HTLV-II, DNA samples were also amplified with HTLV-II specific primers and no evidence of HTLV-II infection was observed. None of the subjects seroconverted according to conventional serological tests during the 2 year follow-up period. The 10 seronegative subjects belonging to the sexual risk group were negative for both HIV 1 and HTLV-I in polymerase chain reaction assays. We conclude that not only HIV 1, but also HTLV-I is a widely spread infection in intravenous drug abusers and sexually active high risk individuals in Argentina.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of HTLV-I DNA in Blood from Patients with Multiple Sclerosis

AIDS Research and Human RetrovirusesVol. 6, No. 11 Absence of HTLV-I DNA in Blood from Patients with Multiple SclerosisGorm Lisby, Jette Frederiksen, Jes Olesen, and Marvin S. ReitzJr.Gorm LisbySearch for more papers by this author, Jette FrederiksenSearch for more papers by this author, Jes OlesenSearch for more papers by this author, and Marvin S. ReitzJr.Search for more papers by this authorPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1990.6.1219AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Absence of HTLV-I DNA in Blood from Patients with Multiple Sclerosis." , 6(11), p. 1219FiguresReferencesRelatedDetails Volume 6Issue 11Nov 1990 To cite this article:Gorm Lisby, Jette Frederiksen, Jes Olesen, and Marvin S. ReitzJr..Absence of HTLV-I DNA in Blood from Patients with Multiple Sclerosis.AIDS Research and Human Retroviruses.Nov 1990.1219-1219.http://doi.org/10.1089/aid.1990.6.1219Published in Volume: 6 Issue 11: March 16, 2009PDF download

Adult T-cell leukaemia/lymphoma in Brazil and its relation to HTLV-1

In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in Brazil the main features were lymphadenopathy, hepatosplenomegaly, hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had irregular nuclei. The series included the youngest patient with ATLL so far (18 months). Analysis with monoclonal antibodies showed a mature T-cell phenotype (CD4 +, CD8 -). Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were found in eleven patients. In the other three HTLV-I DNA could not be demonstrated even by means of the polymerase chain reaction; they therefore had HTLV-I-negative ATLL. This report of ATLL in Brazil corroborates serological reports that HTLV-I may be endemic in some parts of that country. Follow-up studies are required to identify precisely the main route of transmission of HTLV-I in South America and the risk factors for the development of ATLL in carriers.