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As the prevalence of viral infection in body, human T‐cell leukemia virus type 1 (HTLV‐1) is receiving increasing attention. Research on the corresponding virus models is of great significance to tackle the challenges of understanding HTLV‐1 development and treatment. This paper focuses on the dynamic analysis for a stochastic model with nonlinear cytotoxic T lymphocyte (CTL) response, which is driven by Ornstein–Uhlenbeck (OU) process to model the progression of HTLV‐1 in vivo. Rich dynamic behaviors such as the extinction of infected CD4+ T cells (ITCs), stationary distribution (SD), probability density, and finite‐time stability (FTS) of the model are established to reveal the interaction of cell populations. The optimal therapeutic strategy based on the cost‐benefit viewpoint is further obtained. Finally, illustrative numerical simulations are represented to corroborate the effectiveness of treatment and the ambient perturbation's impact that strengthening the noise strength can lead to rapid virus clearance. [ABSTRACT FROM AUTHOR]

Background: Human T‐lymphotropic virus Type 1 (HTLV‐1) is a retrovirus that is endemic in some regions of the world. It is known to cause several diseases like adult T‐cell leukemia (ATL) and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Serology and molecular methods have been used to detect this virus. Of these, enzyme‐linked immunosorbent assay (ELISA) is used as a primary screening method and this is usually followed by western blotting (WB) and polymerase chain reaction (PCR) methods as confirmatory tests. We conducted a systematic review of the different techniques used in the diagnosis of HTLV‐1 infection. Materials and Methods: Our search was limited to original papers in the English language from 2010 to 2018 using several databases including Pubmed, Scopus, Google Scholar, Iranmedex, and Scientific Information Database. A manual search of references provided in the included papers was also performed. Results: Of 101 electronically searched citations, 43 met the inclusion criteria. ELISA is commonly used for qualitative and screening detection, and WB and PCR techniques are used to confirm infection. Conclusion: Among all the reported methods for detection of HTLV‐1, only serological and molecular tests are used as the most common technical assays for HTLV‐1. The ELISA assay, without a confirmatory test, has several limitations and affect the accuracy of the results. Owing to the prevalence of HTLV‐1 and limitations of the current detection methods, further evaluation of the accuracy of these methods is needed. There are new opportunities for applying novel technological advances in microfluidics, biosensors, and lab‐on‐a‐chip systems to perform HTLV‐1 diagnostics. [ABSTRACT FROM AUTHOR]

This paper is concerned with Hopf bifurcation and its stability for the model related to the disease of human T‐cell lymphotropic virus type I (HTLV‐I). In fact, we are considering Hopf bifurcation of the system because it plays an important role in indicating when the disease can return to a steady state condition. The model consists of CD4+ T‐cell subsets of healthy, latently infected, and actively infected cells, as well as for leukemia cells. Latently infected T‐cells may harbor the virus for several years until they become activated and able to infect susceptible T‐cells. In this model, we apply techniques such as the center manifold and normal‐form theorem to simplify bifurcating and the dimension of the dynamical system. The results are applied to clinical data as an example. [ABSTRACT FROM AUTHOR]

In this paper, we propose an improved human T‐cell leukemia virus type 1 infection model with mitotic division of actively infected cells and delayed cytotoxic T lymphocyte immune response. By constructing suitable Lyapunov functional and using LaSalle invariance principle, we investigate the global stability of the infection‐free equilibrium of the system. Our results show that the time delay can change stability behavior of the infection equilibrium and lead to the existence of Hopf bifurcations. Finally, numerical simulations are conducted to illustrate the applications of the main results. [ABSTRACT FROM AUTHOR]

In this paper, the dynamics of stochastic human T‐cell leukemia virus type I (HTLV‐I) infection model with cytotoxic T lymphocyte (CTL) immune response is investigated. First, we show that the stochastic model exists as a unique positive global solution originating from the positive initial value. Second, we demonstrate that the stochastic model is stochastically permanent and stochastically ultimately bounded for any positive initial value. Third, we establish sufficient conditions for the existence of ergodic stationary distribution of the stochastic model. Fourth, the threshold R0∗ between extinction and persistence of the virus is obtained. Finally, numerical simulations are carried out to illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

HTLV-1-associated infective dermatitis (HAID) is the main paediatric manifestation of human T-cell lymphotropic virus type 1 (HTLV-1). It is characterised by a chronic exudative eczematous eruption and persistent infection with Staphylococcus aureus (SA) and beta-haemolytic streptococci (BHS). Prevalence is highest in the Caribbean and Brazil; however, cases have been reported in other HTLV-1 endemic regions. Approximately 20 million people worldwide are infected with HTLV-1 and only 5-10% suffer from disease. Other manifestations include adult T-cell leukaemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). HAID may also progress to ATLL or TSP/HAM. Treatment options are limited to prolonged antibiotic therapy. The aim of this paper is to review existing evidence and propose new theories on the pathogenesis of HAID. The current view is that HTLV-1 infection is required and in susceptible individuals leads to immune dysregulation with subsequent immunosuppression and superinfection with SA and BHS. Evidence suggests that host, environment and genetic factors may play a causative role. Genetic factors within ethnic groups determine host immune response and carrier state or disease manifestation of HTLV-1 infection. Increased IgE levels may contribute to the SA and BHS superinfection in HAID. Additionally, the possible impact of filaggrin, skin proteinase dysregulation, Langerhans cell dysfunction and TH2 chemokines is highlighted. More than 45 years since the discovery of HAID, the exact pathogenesis is still not fully understood. Further research is still needed to clearly elucidate the exact pathogenic mechanism of HAID. [ABSTRACT FROM AUTHOR]

The Akt signaling pathway is important for survival and growth of cancer cells. In the present paper we show that the Akt signaling pathway is constitutively activated in human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines and in primary adult T-cell leukemia (ATL) cells. Curcumin, a natural compound present in turmeric, has been studied vigorously as a potent chemopreventive agent for cancer therapy because of its inhibitory effect on proliferation and induction of apoptosis in several tumor cell lines. We investigated the effect of curcumin on Akt activity in HTLV-I-infected T-cell lines and primary ATL cells. Phosphorylated PDK1 is an activator of Akt by phosphorylating Akt. Curcumin reduced phosphorylation of PDK1 and inhibited constitutive activation of Akt. Curcumin activated glycogen synthase kinase (GSK)-3β, a downstream target of Akt kinase, by inhibiting phosphorylation of this protein. Curcumin reduced the expression of cell cycle regulators, cyclin D1 and c-Myc proteins, which are both degraded by activated GSK-3β. Our results suggest that activation of the Akt signaling pathway plays an important role in ATL cell survival, and that curcumin may have anti-ATL properties mediated, at least in part, by inhibiting Akt activity. We propose that Akt-targeting agents could be useful for the treatment of ATL. In this regard, curcumin is a potentially promising compound for the treatment of ATL. ( Cancer Sci 2006; 97: 322 – 327) [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is a redox gasotransmitter. It has been shown that H2S has a key role in host antiviral defense by inhibiting interleukin production and S‐sulfhydrating Keap1 lead to Nrf2/ARE pathway activation. However, it is yet unclear whether H2S can play an antiviral role by regulating autophagy. In this study, we found that exogenous H2S decreased the expression of human T‐cell leukemia virus type‐1 (HTLV‐1) protein and HTLV‐1 induced autophagosomes accumulation. Transmission electron microscope assays indicated that autophagosomes accumulation decreased after H2S administration. HTLV‐1‐transformed T‐cell lines had a high level of CSE (H2S endogenous enzyme) which could be induced in Hela by HTLV‐1 infection. Immunoblot demonstrated that overexpression of CSE inhibited HTLV‐1 protein expression and autophagy. And we got the opposite after CSE knockdown. Meanwhile, H2S could not restrain the autophagy when ATG4B had a mutant at its site of 89. In a word, these results suggested that H2S modulated HTLV‐1 protein expression via ATG4B. Therefore, our findings suggested a new mechanism by which H2S defended against virus infection. [ABSTRACT FROM AUTHOR]

Objective: Human T‐cell lymphotropic virus 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive myelopathy. A high proviral load (PVL) is one of the main risk factors for HAM/TSP. Recently, it was shown that raltegravir could inhibit cell‐free and cell‐to‐cell transmission of HTLV‐1 in vitro. Given the substantial clinical experience in human immunodeficiency virus infection and its excellent safety profile, this agent may be an attractive therapeutic option for HAM/TSP patients. Methods: Sixteen subjects with HAM/TSP received raltegravir 400 mg orally twice daily in an initial 6‐month treatment phase, followed by a 9‐month post‐treatment phase. HTLV‐1 PVLs were assessed using droplet digital PCR from the PBMCs every 3 months, and from the CSF at baseline, month 6, and month 15. We also evaluated the ability of raltegravir to regulate abnormal immune responses in HAM/TSP patients. Results: While a downward trend was observed in PBMC and/or CSF PVLs of some patients, raltegravir overall did not have any impact on the PVL in this HAM/TSP patient cohort. Clinically, all patients' neurological scores and objective measurements remained relatively stable, with some expected variability. Immunologic studies showed alterations in the immune profiles of a subset of patients including decreased CD4+CD25+ T cells and spontaneous lymphoproliferation. Interpretation: Raltegravir was generally well tolerated in this HAM/TSP patient cohort. A subset of patients exhibited a mild decrease in PVL as well as variations in their immune profiles after taking raltegravir. These findings suggest that raltegravir may be a therapeutic option in select HAM/TSP patients. Clinical Trial Registration Number: NCT01867320. [ABSTRACT FROM AUTHOR]

Human T‐cell leukemia virus type 1 (HTLV‐1) is an oncogenic retrovirus that causes adult T‐cell leukemia (ATL). The viral protein HTLV‐1 basic leucine‐zipper factor (HBZ), which is constitutively expressed in all ATL patient cells, contributes toward the development of ATL; however, the underlying mechanism has not been elucidated yet. Here, we identified HS‐1‐associated protein X‐1 (HAX‐1) as a novel binding partner of HBZ. Interestingly, HAX‐1 specifically associated with HBZ‐US, but not HBZ‐SI, in the cytoplasm. HBZ suppressed the polyubiquitination levels of HAX‐1 protein by inhibiting the association HAX‐1 with F‐box protein 25 (FBXO25), which is a member of the SCF E3 ubiquitin ligase complex, and promoted the stabilization of HAX‐1 levels. In fact, the protein levels of HAX‐1 were significantly increased in HTLV‐1 infected and the overexpressing HBZ in uninfected T‐cell lines. Enhanced HAX‐1 correlated well to suppression of caspase 9 processing, suggesting that HBZ may contribute to the enhancement of antiapoptotic function for HAX‐1. Our results revealed a role for HBZ on HAX‐1 stabilization by abrogating the ubiquitination‐mediated degradation pathway, which may play an important role in understanding the potential mechanisms of HTLV‐1 related pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Individuals infected with the human T‐cell lymphotropic virus type 1 (HTLV‐1) commonly present skin lesions, which may be a warning sign for the diagnosis of infection. This study describes the most prevalent skin manifestations in HTLV carriers attended at the clinic of Núcleo de Medicina Tropical (NMT) of the Universidade Federal do Pará (UFPA) in Belém, Pará, Brazil. Methods: This is a study of a series of cases of patients infected with human T‐cell lymphotropic virus types 1 and 2 (HTLV‐1/2) treated at NMT UFPA between 1999 and 2016. A descriptive analysis of data was applied. Results: Among 788 surveyed medical records in the service, 15.10% (n = 119) were referred to the dermatology clinic. From the series of cases that presented with skin lesions, 66.39% were female and 33.61% were male, and the average age of this group was 48 years. There was a predominance of patients with noninfectious inflammatory manifestations (64.2%), followed by infectious ones (24.6%), and 1.58% with lymphoproliferative diseases. As for the group of lesions, 45.26% of the erythematous‐squamous type were observed, followed by dyschromia (24.21%), and eczematous (14.74%). One patient with a diagnosis of adult T‐cell leukemia/lymphoma, another with parapsoriasis, and four with infective dermatitis are highlighted. Conclusion: Skin disorders in the HLTV positive patient are important causes of referral to the dermatologist with etiological and skin lesions groups diversity. In the series of cases studied, lymphoproliferatives diseases and infective dermatitis associated with HTLV‐1 were presented as a challenge for the diagnosis and clinical management of these patients. [ABSTRACT FROM AUTHOR]

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Background and objectives: Donated blood is not currently screened for human T‐cell lymphotropic virus (HTLV) in South Africa. Several small studies have detected HTLV‐1 in South Africa, but prevalence by geographic region or population group is unavailable. Materials and Methods: We performed a large seroprevalence study of South African blood donors during 3 months in 2013. All geographic regions except the Western Cape were included, and Black and Coloured (local term for mixed race) donors were oversampled. Identity‐unlinked plasma samples were screened with the Abbott Prism HTLV‐1/2 assay, and repeatedly reactive samples were tested by the Inno‐LIA HTLV‐1/2 Score confirmatory assay. Odds ratios were calculated with multivariable logistic regression. Results: Of 46 752 donors tested, 133 (0·28%) were initially reactive, 111 (0·24%) repeatedly reactive and 57 (0·12%) confirmed positive for HTLV‐1; none were HTLV‐2 positive. Prevalence was 0·062% weighted to annual blood donations but highly concentrated in the Black population group (OR = 20·24 CI: 2·77–147·88); higher in females than males (OR = 1·81 CI: 1·06–3·08); and in donors aged >50 years compared to ages 16–19 (OR = 6·4 CI: 2·95‐13·86). After controlling for age, sex and population group, there was no difference in prevalence between new and repeat blood donors or among geographic regions within South Africa. Conclusions: We conclude that HTLV‐1 infection is widespread among the Black population of South Africa and its epidemiology is similar to other endemic areas. Because South Africa is increasing its recruitment of Black blood donors, the implications for blood screening require further consideration. [ABSTRACT FROM AUTHOR]

The article discusses a study on the cost-effectiveness of human T lymphotropic virus type 1 (HTLV-1) antenatal screening in Great Britain. Topics covered include ways HTLV-1 infection occurs, estimated number of HTLV-1 carriers in Great Britain, and the use of decision tree modelling to assess the cost-effectiveness of HTLV-1 antenatal screening.

SUMMARY Objectives Blood donors in Canada have been tested for Human T-Cell Lymphotropic Virus ( HTLV) since 1990. We report the epidemiology, risk factors and lookback/traceback of HTLV-positive donors/recipients. Methods The annual HTLV rate was calculated from 1990 to 2010. Residual risk was estimated as the product of incidence and window period. Twenty-nine HTLV-positive donors and 116 matched controls (ratio 1 : 4) were interviewed about risk factors. For HTLV-positive donations, lookback investigations involved identification of all previous donations, and attempting to locate and test recipients. Traceback was initiated when transfusion transmission was queried for HTLV-positive blood recipients. All donors of products that the recipient received were identified, with an attempt to locate and test them. Results The HTLV rate decreased from 9·35 per 100 000 donations in 1990 to 1·11 in 2010. The residual risk of infection was 1 in 7·6 million donations. In logistic regression birth overseas ( OR 18·7), history of sexually transmitted diseases ( OR 32·9), sex with unknown background ( OR 5·4) and blood transfusion ( OR 8·9) were significant predictors. In the lookback study, of 109 HTLV-positive donors, 508 components were transfused, of whom 147 recipients were tested and 18 (12%) were positive. All were transfused prior to the implementation of donor testing. Twenty-three traceback investigations were requested involving 324 transfused untested products,of whom 219 (67·6%) of donors were tested and 13 (6%) were positive for HTLV. Conclusions With testing of the blood supply, the risk from HTLV is very low and while most HTLV-positive donors have risk factors, deferrable risk is rare. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus type 1 ( HTLV-1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well-known complication, adult T-cell leukemia/lymphoma ( ATLL). HTLV-1 associated bronchiolo-alveolar disorder ( HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV-1 carriers. The reported clinico-pathological patterns of HABA are diffuse panbronchiolitis ( DPB) and lymphoid interstitial pneumonia ( LIP). We here report three cases of HTLV-1 carriers showing miliary micro-nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro-nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus-1 (HTLV-1) causes adult T-cell leukemia/lymphoma, which is an aggressive peripheral T-cell neoplasm. Insufficient T-cell response to HTLV-1 is a potential risk factor in adult T-cell leukemia/lymphoma. Efficient induction of antigen-specific cytotoxic T lymphocytes is important for immunological suppression of virus-infected cell proliferation and oncogenesis, but efficient induction of antigen-specific cytotoxic T lymphocytes has evaded strategies utilizing poorly immunogenic free synthetic peptides. Here, we examined the efficient induction of an HTLV-1-specific CD8+ T-cell response by oligomannose-coated liposomes (OMLs) encapsulating the human leukocyte antigen (HLA)-A*0201-restricted HTLV-1 Tax-epitope (OML/Tax). Immunization of HLA-A*0201 transgenic mice with OML/Tax induced an HTLV-1-specific gamma-interferon reaction, whereas immunization with epitope peptide alone induced no reaction. Upon exposure of dendritic cells to OML/Tax, the levels of CD86, major histocompatibility complex class I, HLA-A02 and major histocompatibility complex class II expression were increased. In addition, our results showed that HTLV-1-specific CD8+ T cells can be efficiently induced by OML/Tax from HTLV-1 carriers compared with epitope peptide alone, and these HTLV-1-specific CD8+ T cells were able to lyse cells presenting the peptide. These results suggest that OML/Tax is capable of inducing antigen-specific cellular immune responses without adjuvants and may be useful as an effective vaccine carrier for prophylaxis in tumors and infectious diseases by substituting the epitope peptide. We examined the efficient induction of HTLV-1-specific CD8+ T-cell response by oligomannose-coated liposomes (OMLs) encapsulating the HTLV-1 Tax-epitope (OML/Tax) in vivo and ex vivo. Our results indicated that OML/Tax efficiently induced the HTLV-1-specific CD8+ T-cell response without adjuvant, suggesting that the efficient antigen delivery system can be exploited to develop a therapeutic vaccine model against tumors and infectious diseases. [ABSTRACT FROM AUTHOR]

The article discusses several infectious diseases research including study on dengue fever in Venezuela, cutaneous lesions of adult T-cell leukemia, and patient with down syndrome. Topics discussed include cases of lung disease and congestion of abdominal viscera, t cell leukemia/lymphoma (ATL) caused by human t-cell lymphotropic virus type-1 (HTLV-1), and chagas disease constituted as public health issues.

The objective of this study was to perform lookback study in recipients of blood components from human T-lymphotropic virus (HTLV) seropositive donors. HTLV-1/2 may be transmitted by blood transfusion. Brazil is an endemic area for the virus and its screening in blood donors is mandatory since 1993. Hemominas Foundation (HF) is the public transfusion centre in Minas Gerais, Brazil. Data on HTLV-1/2 seropositive donors and recipients from 1993 to 2004 were obtained at HF and 24 contracting hospitals. From 1993 to 2004, HTLV-1/2 enzyme immunoassay (EIA) was performed in 918 678 donations of approximately 422 600 blood donor candidates. Of these, 456 donors (0·1%) were reactive and confirmed by Western blot (WB): 449 HTLV-1 and 7 HTLV-2. Sixty-six (14·5%) were repeat donors and had 194 blood cellular components produced from their previous donations. Of the distributed components, 119/146 (81·5%) had the recipient traced, with a total of 114 individuals. Of these, only 13 recipients were tested: six (46%) were HTLV-1 positive (four recipients of red cell units, two of platelets) and seven (54%) were negative (six of red cell units and one of platelets). Eleven did not respond and 62/114 (54·0%) were deceased. Another 28/114 (25·0%) could not be located. All six seropositive HTLV-1 recipients identified had no symptoms suggestive of HTLV-1-associated diseases. Acellular components, when used alone, were not associated with HTLV seropositivity. HTLV-1 transmission by cellular blood components occurred before screening for the virus was introduced. Haemovigilance was difficult to perform due to unavailability of computer systems before 1999 and to inadequate medical records at hospitals. [ABSTRACT FROM AUTHOR]

Background Infective dermatitis (ID) is a rare dermatologic condition of childhood that has been linked to human T-cell lymphotropic virus type 1 (HTLV-1). Objective To analyze the clinical and laboratory features associated with adult-onset ID linked to HTLV-1. Methods From December 1995 to December 2007, four patients with ID were followed in the dermatology outpatient clinic of the “Hospital das Clínicas” of the University of São Paulo Medical School, São Paulo, Brazil. Epidemiologic data were collected and dermatologic examination was performed. Patients were submitted to histopathologic, hematologic, virologic, and immunologic investigations. Results All patients had a diagnosis of ID according to previously established criteria, despite being adults. HTLV-1 infection was demonstrated by enzyme-linked immunosorbent assay, Western blotting assays, and polymerase chain reaction. The male to female ratio was 1 : 3 and the median age at diagnosis was 42 years. The cutaneous manifestations were erythematous, scaly, and crusted lesions in all patients, and ichthyosis in three of the four cases. Histopathologic study showed lymphocytic epidermotropism in two cases. The median proviral load was 281 copies/10,000 peripheral blood mononuclear cells. Immunodeficiency was not observed in any case. The therapies used were antimicrobials, corticosteroids, and phototherapy. Conclusions Although many authors have considered ID to be a form of childhood dermatitis, we have described four cases that fulfilled the major criteria for ID, except for onset in adulthood. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor α (TNFα) inhibitors are widely used successfully as immunomodulatory agents in various autoimmune diseases. They primarily target the direct pro-inflammatory effect of TNFα. They have also been found to be critical for T-cell viability and activation. In this study we evaluated the effect of infliximab treatment under different in vitro stimulatory conditions of naive human cord blood T-cells and adult peripheral blood mononuclear cells (PBMC). PBMC and negatively selected cord blood naive human T-cells were stimulated with αCD3 with or without αCD28 co-stimulation. The role of in vitro infliximab treatment was evaluated in relation to transforming growth factor-β1 (TGF-β1) under the above different stimulatory conditions. Anti-TNFα treatment with infliximab significantly suppressed proliferation of adult and cord blood T-cells ( P < 0.013) during suboptimal stimulatory conditions. Infliximab prevented division of naive CD4+ and CD8+ T-cells and consequently also activation induced cell death, which was induced after three cell divisions. Interleukin (IL)-2 secretion was significantly decreased during infliximab treatment of suboptimally stimulated T-cells ( P < 0.05) while TGF-β1 levels were unchanged. Strikingly, the anti-proliferative effect of infliximab was overcome by the administration of anti-TGF-β1 or by the addition of exogenous IL-2. Interestingly, CD28 mediated co-stimulation restored the proliferative response in a dose–responsive manner during infliximab treatment. Finally, exogenous TNFα administration during suboptimal stimulation reduced the inhibitory effect of TGF-β1 upon proliferation ( P < 0.03). These results demonstrate that anti-TNFα treatment is primarily working upon T cells under low stimulatory conditions and probably through TGF-β1. [ABSTRACT FROM AUTHOR]

Adult T-cell leukaemia (ATL) is caused by human T-cell leukaemia virus type I (HTLV-I). It has been suggested that cytokines play a role in the development and in the neoplastic cell growth of ATL. However, the precise mechanism involved in this process still remains unclear. Interleukin-21 (IL-21) and its receptor (IL-21R) have been recently described. In this study, we examined the expression of IL-21R and the effect of IL-21 on ATL cells. Real-time reverse transcription polymerase chain reaction showed that HTLV-I-infected cell lines and primary ATL cells expressed IL-21R mRNA. Cell surface expression of IL-21R on these cells was confirmed by flow cytometric analysis using a newly developed monoclonal antibody against human IL-21R. In contrast to the expression of IL-21R, IL-21 mRNA was scarcely detectable in these cells. Notably, IL-21 induced the proliferation of ATL-43T and ED-40515(+) cells, both of which were derived from leukaemic cell clones of ATL. Concerning the intracellular signalling pathways, IL-21 activated the phosphorylation of the signal transducers and activators of transcription (STAT)3 and STAT5. Taken together, these findings provide the first evidence that ATL cells express functional IL-21R, suggesting that it may contribute to the pathophysiology of ATL. In addition, the IL-21/IL-21R system may represent a new target for the treatment of ATL. [ABSTRACT FROM AUTHOR]

Background and objectives An age- and gender-specific distribution characterizes human T-cell lymphotrophic virus type-I (HTLV-I) seropositivity in Guadeloupe (French West Indies). Further epidemiological studies are required to identify other possible risk factors associated with this retroviral infection. Materials and methods A nested case-control study was conducted between 1997 and 1999 among blood donors. A total of 102 HTLV-I-positive subjects were matched (at a ratio of 1:3) by gender, age (±5 years) and donor status (new or regular) to 306 HTLV-I-negative controls. Information was obtained through a questionnaire assessing both environmental and behavioural variables. Results Factors independently associated with HTLV-I infection included a low level of education [odds ratio (OR) 6.61, confidence interval (CI) 2.89-15.15], black ethnicity (OR 3.28, CI 1.01-10.65), two or more sex partners in the previous 3 years (OR 2.43, CI 1.16-5.10), early age at first sexual intercourse (0.84 risk reduction per additional year, CI 0.76-0.93), a history of sexually transmitted diseases (OR 2.29, CI 1.05.34) and positive Chlamydia serology (OR 1.95, CI 1.03-3.68). Conclusion These data provide a wide spectrum of features associated with HTLV-I seropositivity, especially sexual risk factors. It strongly suggests that heterosexual intercourse is an important route of HTLV-I transmission in Guadeloupe, even among low-risk populations such as blood donors. [ABSTRACT FROM AUTHOR]

Adult T-cell lymphoma (ATL-L) developing initially in the meninges is rare. An autopsy case of ATL-L with an acute onset of meningitis and generalized lymphadenopathy in association with a cervical cord schwannoma is reported here. A 78-year-old woman with sensori-motor weakness of both arms over a 1-year period, developed febrile episodes and drowsiness with neck stiffness. Lumbar puncture revealed an increased protein content (161 mg/dL) and increased cell count (463/3) consisting of 99% of lymphocytes which contained atypical lymphocytes with multilobulated nuclei (‘flower cells’), which are characteristic of ATL-L. Viral titers were positive only for HTLV-I antibodies (serum 3 640: CSF 3 16). Biopsy of an enlarged retroperitoneal lymph node revealed malignant lymphoma of the T-cell type. Brain MRI was negative, whereas an intradural extramedullary mass was found at the C4 level. With a diagnosis of ATL-L stage IV, chemotherapy was commenced, which was effective in reducing the generalized lymphadenopathy as well as the cervical mass and restoring the CSF findings to normality. The cervical cord mass was verified to be a solitary schwannoma, and ATL-L involvement was found not only in the leptomeninges, but also within the cervical cord schwannoma. [ABSTRACT FROM AUTHOR]

Large lymphocytes with basophilic cytoplasm and cleaved/cerebriform nuclei called flower cells have been described in human T-lymphotrophic virus type I (HTLV-I) seropositive individuals and may be precursors of adult T-cell leukaemia (ATL). A cohort of 546 HTLV-seropositive former blood donors, 32 HTLV-positive sexual partners of these donors and 799 HTLV-seronegative controls has been followed as part of the Retrovirus Epidemiology Donor Study. A novel methodology was developed to systematically review peripheral blood slides from these subjects for HTLV-related lymphocyte abnormalities, using an algorithm based on morphologic features to objectively identify flower cells. The algorithm included: absence of azurophil granules; nuclear chromatin condensation; cell size >1.5 small lymphocytes; nuclear to cytoplasmic ratio >80%; and presence of nuclear folding/lobulation. Peripheral slides from subjects were screened by a medical technologist blinded to HTLV status. 6.8% of HTLV-I subjects (P = 0.0001 versus seronegatives), 0.9% of HTLV-II subjects and 1.1% of seronegatives were confirmed to have cells classified as flower cells by two haematologists using objective criteria, and blinded to serostatus. Despite the higher prevalence of flower cells in HTLV-I positives, no clinical correlations were found. Longitudinal follow-up may yield higher rates of cellular abnormalities as the sequelae of HTLV infection develop. [ABSTRACT FROM AUTHOR]

This article focuses on the cutaneous T-cell lymphoma (CTCL). CTCL represents a spectrum of diseases composed of malignant clonal helper T lymphocytes. CTCL is twice as common in men than in women, and African-Americans have twice the incidence compared with Whites. The incidence has increased from 0.19 cases per 1000,000 in 1973 to 0.43 cases per 100,000 in 1984. The hypothesis of a retroviral cause of CTCL was at the forefront of etiologic research efforts after the human T-cell lymphotrophic virus type-I (HTLV-I), a type C retrovirus was found to have a casual relation to adult T-cell leukemia/lymphoma; however, most CTCL patients have negative serologic tests for the presence of HTLV-I/II.

Background and Objectives Certain patient ethnic groups may require blood components from donors under-represented in the UK donor population. Selective recruitment of Afro-Caribbean donors is therefore necessary but was considered to pose an increased risk of human T-cell leukaemia/lymphoma virus (HTLV) infection. To assess this a seroprevalence study of HTLV was undertaken in Afro-Caribbean and Caucasian donors. Materials and Methods Sera from 1100 Afro-Caribbean and 1100 Caucasian donors were tested for antibody to HTLV. Reactive samples were confirmed for specificity using an algorithm comprising two additional assays and polymerase chain reaction (PCR) where possible. Results Six Afro-Caribbean donors (0·55%) were considered to be infected with HTLV I. Conclusion Donor selection in this case caused a significantly elevated prevalence of HTLV infection and serves as a warning of the need for care in the design of policies for selective donor recruitment. [ABSTRACT FROM AUTHOR]

Studies the individuals infected with human T-cell lymphotropic virus type I (HTLV-I) in Brazil. Variety of T-cell epitopes that are recognized in the context of specific classes I and II human leucocyte antigen (HLA) molecules expressed by HTLV-I infected-T-cells; Determination of HLA-A, -B and -DR specificities by polymerase chain reaction with sequence-specific primers; Association of HLA-DR8 with adult T-cell leukemia/lymphoma.

The article focuses on human T cell lymphotropic virus-I (HTLV-I) infection and adult T cell leukemia. HTLV-I, the first discovered, is a C type retrovirus and a member of the group of transforming retroviruses. Cutaneous lesions are pleomorphic and resemble those of cutaneous T cell lymphoma, mycosis fungoides (MF) and are characterized by papules, nodules, and plaques but unlike MF they spread rapidly in the skin and disseminate to regional and central lymph nodes and to viscera. Adult T cell leukemia-lymphoma responds to combination chemotherapy but, remissions are usually short-lived and patients die within one year or two from infection or from their disease.