BVDV, BHV-1 and BLV antibodies in dromedary camels of Turkey kept without and with ruminants.

Camels are the only animals bred to sustain the tradition of wrestling in Turkey and are reared within a limited set of geographic areas. Farmers of such animals may also be engaged in ruminant breeding. The current research was aimed at documenting bovine viral diarrhoea virus (BVDV), bovine herpesvirus-1 (BHV-1), and bovine leukaemia virus (BLV) infections in sera collected from dromedary camels in four different geographical regions of Turkey during the years 2019-2021. All samples were tested for BVDV, BHV-1 and BLV antibodies as well as BVDV antigen by ELISA. Antibodies against BVDV were found in 16.8% of the camel sera tested. However, none of the camels sampled were positive in terms of BHV-1 and BLV antibodies as well as BVDV antigen. The prevalence was observed higher in the herds in which ruminants were raised in addition to camels (OR = 4.583, 95% CI, 1.298-16.182), (p = 0.018), while the prevalence was observed lower in the herds in which only camels were raised. This study showed that BVDV infection was more prevalent than BHV-1 and BLV infections in Turkish dromedary camels. Herewith, the camels, being a susceptible species to numerous viral ruminant diseases, may also serve as an important source of BVDV infection for other ruminant animals in the same flock.

Eficacia y seguridad de blinatumomab en pacientes con diagnóstico de leucemia linfoblástica aguda de precursores de células b, philadelphia negativo, en recaída y/o refractario / Efficacy and safety of blinatumomab in patients diagnosed with acute lymphoblastic leukemia of b-cell precursors, negative philadelphia, relapse and / or refractory

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de blinatumomab; comparado con quimioterapia de rescate (metotrexato, vincristina, etopósido) para el tratamiento de pacientes con diagnóstico de leucemia linfoblástica aguda de precursores de células B, Philadelphia negativo, que hayan recaído o cuya enfermedad haya sido refractaria al tratamiento. La leucemia linfoblástica aguda (LLA) es una neoplasia maligna con proliferación de células precursoras linfoides. Solo el 20 % de las LLA se presentan en adultos. En pacientes de 25 a 59 años de edad, la sobrevida es, aproximadamente, 40 % y en adultos mayores es menor al 20 %. Pueden identificarse tres tipos de LLA: de linaje ambiguo, de células B (LLA-B) y de células T. La LLA-B es el tipo más frecuente (80-85 % de los casos). El pronóstico de los pacientes con LLA-B empeora con la presencia de alteraciones genéticas, como la translocación BCR/ABL; también llamado: cromosoma Philadelphia (Ph) y en los casos recurrentes y/o refractarios (R/R). Estos pacientes requieren de tratamientos más agresivos para lograr la remisión. No obstante, la curación y la sobrevida libre de enfermedad a largo plazo es posible en menos del 25 % de los casos y las remisiones son de corta duración. TECNOLOGÍA SANITARIA DE INTERÉS: Blinatumomab es un anticuerpo bi-específico de células T desarrollado para el tratamiento de neoplasias hematológicas originadas en el linaje de células B, especialmente en casos de LLA-B y linfoma no Hodgkin (Sanford M. 2015) . Aunque al momento de su aparición blinatumomab fue considerado un medicamento revolucionario, se advierte el riesgo de complicaciones potencialmente fatales, como: neutropenia, infecciones, síndrome de liberación de citoquinas o toxicidad neurológica. OBJETIVO: Evaluar la eficacia y seguridad del uso de blinatumomab, en comparación con quimioterapia de rescate en pacientes con LLA-B, Ph(-) en recaída y/o refractario. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de blinatumomab en el tratamiento de pacientes con diagnóstico de leucemia linfoblástica aguda de precursores de células B, Philadelphia negativo, en recaída y/o refractario. Se realizó tanto una búsqueda sistemática como una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica (GPC) y evaluaciones de tecnologías sanitarias (ETS). RESULTADOS: La presente evaluación de tecnología sanitaria muestra la evidencia encontrada luego de una búsqueda sistemática, con respecto a la eficacia (sobrevida global, remisión completa de enfermedad, y calidad de vida) y seguridad (incidencia de eventos adversos) de blinatumomab, comparado con quimioterapia de rescate en pacientes adultos con LLA-B, Ph(-) R/R. Al respecto, se identificaron dos guías de práctica clínica (GPC) elaboradas por la European Society for Medical Oncology (ESMO) en 2016 y la National Comprehensive Cancer Network (NCCN) en 2019; tres evaluaciones de tecnologías sanitarias (ETS) elaboradas por la Canadian Agency for Drugs and Technologies in Health (CADTH) en 2016, el Scottish Medicines Consortium (SMC) en 2016 y el National Institute for Health and Care Excellence (NICE) 2017; y, tres publicaciones de los años 2017 y 2018 del ensayo clínico aleatorizado (ECA) fase III TOWER; los cuales responden directamente a la PICO establecida en el presente dictamen. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se presenta la evidencia recabada sobre la eficacia y seguridad blinatumomab en comparación con la quimioterapia de rescate en pacientes adultos con LLA-B, Ph(-), R/R. Se recolectó la evidencia de dos GPC, tres ETS y un ECA fase III. Aunque las GPC y las ETS recomiendan blinatumomab para el tratamiento de pacientes adultos con LLA-B, Ph(-), R/R, la confianza en la evidencia utilizada para formular esta recomendación está limitada por: i) la poca cantidad de evidencia primaria disponible: dos ECA fase II (MT 103-211 y MT 103-206) y un ECA fase III (TOWER), ii) los detalles de las recomendaciones de las GPC y ETS difieren entre sí a pesar de provenir prácticamente de la misma evidencia, iii) El ECA TOWER (principal estudio para responder la pregunta PICO) presenta varias limitaciones que afectan la validez de sus resultados, y, iv) la incertidumbre en la evidencia disponible solo logra que blinatumomab sea considerado por las ETS solo como una alternativa de tratamiento (por debajo de la participación de EC de nuevos medicamentos) sujeta a acuerdos económicos (para el caso de las ETS) que mejoren su costo-efectividad. Con respecto a lo expuesto previamente, el equipo técnico del IETSI valoró los siguientes aspectos: i) La LLA-B es una enfermedad de mal pronóstico cuando se presenta en adultos y empeora en los casos R/R, ii) La evidencia disponible no asegura que la magnitud de la eficacia de blinatumomab se traduzca en un cambio clínicamente relevante, iii) Toda vez que blinatumomab ha sido recomendado por las ETS, es bajo la condición de reducir del precio de compra blinatumomab a niveles de costo-efectividad aceptables, y, iv) No es posible asumir un perfil de costo-oportunidad favorable para sistemas públicos de servicios de salud como el nuestro porque no se ha encontrado que blinatumomab sea más eficaz o seguro que otros esquemas de quimioterapia de rescate disponibles en EsSalud. Se queda a la espera de futuras publicaciones con mayor tiempo de seguimiento y que superen las limitaciones presentes en la evidencia disponible hasta la fecha. El Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI, no aprueba el uso de blinatumomab para el tratamiento de pacientes adultos con LLA-B, Ph(-), R/R.

No significant HTLV seroprevalence in German people who inject drugs.

BACKGROUND: Although human T-lymphotropic virus (HTLV) is transmitted via the same routes as human immunodeficiency virus (HIV), its worldwide seroprevalence differs drastically because HTLV is transmitted mainly via infected cells rather than free virus. The sharing of needles and other equipment places people who inject drugs (PWID) at particularly high-risk for such blood-borne diseases. METHODS: To validate the methodology used to process and analyze the dried blood spots (DBS) utilized in the study, dried serum spots (DSS) with dilutions of sera from known HTLV infected individuals were analyzed by ELISA and Western blot. DBS collected between 2011 and 2015 from 2,077 PWID in eight German cities recruited by respondent-driven sampling were tested for HTLV-specific antibodies. RESULTS: The validation demonstrated that the use of DSS allowed identification of samples with even low titers of HTLV-specific antibodies, although a confirmatory Western blot with an additional venous blood sample would often be required. Despite numerous HIV and HCV positive individuals being identified within the study population, none tested positive for HTLV. CONCLUSION: While the HIV and HCV prevalences in German PWID are comparable to those in other European countries, the very low prevalence of HTLV reflects the situation in the general population.

Flow cytometric-based protocols for assessing anti-MT-2 IgG1 reactivity: High-dimensional data handling to define predictors for clinical follow-up of Human T-cell Leukemia virus type-1 infection.

The present work provides an innovative methodological approach to assess the anti-HTLV-1 IgG1 reactivity with practical application in clinical laboratory. Serum from non-infected healthy controls (NI) and HTLV-1-infected patients, categorized as asymptomatic (AS), putatively progressing to HTLV-1 associated myelopathy/tropical spastic paraparesis - HAM/TSP (pHAM) or with clinical diagnosis of HAM/TSP (HT) were assayed in two-parallel flow cytometry platforms, referred as: Fix and Fix&Perm protocols. Operating-characteristics analysis indicated that a single pair of attributes ("serum dilution/cut-off") for Fix and Fix&Perm protocols presented excellent performance for the diagnosis of HTLV-1 infection. Conversely, Fix and Fix&Perm protocols displayed weak/moderate overall performances when applied with prognosis purposes of HTLV-1 infection. A panoramic snapshot provided by the reactivity boards revealed clearly the higher sensitivity of Fix&Perm protocol for detecting seropositivity for HT, suggesting that stepwise combinatory criteria would improve the global performance of using a single pair of attributes. Three data mining strategies were tested, including endpoint titer analysis, heatmap assemblage and decision tree analysis. Bi-dimensional heatmap analysis demonstrated that, while the clustering profile of NI vs HTLV-1+ revealed segregation in opposite poles, AS vs HT presented discrete segregation but still displaying an intertwined distribution pattern. The combination of methods for segregating AS from HT displayed a moderate but superior global accuracy (85.7%; LOOCV=71.4%). The comprehensive data analysis support that the combination of methods have improved the performance to the differential diagnosis of AS and HT, with direct association with laboratorial records, including serum cytokine levels and proviral load.

Prevalence of serological ineligibility among blood donors of a Hemotherapy Center in Caxias do Sul, southern Brazil

Introduction: Blood donation should be voluntary, anonymous and altruistic, and the donor should not, directly or indirectly, receive any remuneration or benefit by virtue of donating blood. Like any other therapeutic method, transfusion procedures are not risk free and can expose the patient to a several complications. Serological screening is of great importance to ensure transfusion safety. The present study aimed to estimate the prevalence of serological ineligibility among blood donors from a Hemotherapy Center in Caxias do Sul (RS). Method: An exploratory, descriptive and quantitative study was conducted on data from July 2010 to December 2015 collected at a Hemotherapy Center in Caxias do Sul (RS). Results: During the study period, 14,267 blood donors attended the Hemotherapy Center, of which 9,332 (65.40%) were males and 4,935 (34.60%) were female. Considering only the suitable donors, 12,702 blood donations were performed, 144 (1.13%) presented positive serological tests. The most prevalent positive serology was for hepatitis B (anti-HBc) with 98 cases (0.77%), followed by syphilis with 19 cases (0.15%); Chagas disease, with 10 (0.08%); hepatitis C, with nine (0.07%); and HIV and HTLV, with four (0.03%) reactive samples each. Conclusion: The results presented are important for health surveillance and make it possible to take measures to ensure safe blood stocks (AU)

Development and evaluation of an immunochromatographic assay using a gp51 monoclonal antibody for the detection of antibodies against the bovine leukemia virus

Infection of cattle with bovine leukemia virus (BLV) has been observed and reported worldwide, including in Korea. The onsite identification of infected cattle would help decreasing and eradicating BLV infections on farms. Here, we present a new immunochromatographic assay that employs monoclonal antibodies (MAbs) for the detection of antibodies against BLV in the field. BLV envelope glycoprotein (gp)51 was expressed in E. coli, and MAbs against recombinant BLV gp51 were generated for the development of an immunochromatographic assay to detect BLV antibodies in cattle. The sensitivity and specificity of the assay were determined by comparing these results with those obtained from a standard enzyme linked immunosorbent assay (ELISA). A total of 160 bovine sera were used to evaluate the new immunochromatographic assay. Using ELISA as a reference standard, the relative specificity and sensitivity of this assay were determined to be 94.7% and 98%, respectively. Because of its high sensitivity and specificity, this BLV antibody detection assay would be suitable for the onsite identification of BLV infection in the field.

Expression and Purification of a Novel Computationally Designed Antigen for Simultaneously Detection of HTLV-1 and HBV Antibodies.

Computational tools are reliable alternatives to laborious work in chimeric protein design. In this study, a chimeric antigen was designed using computational techniques for simultaneous detection of anti-HTLV-I and anti-HBV in infected sera. Databases were searched for amino acid sequences of HBV/HLV-I diagnostic antigens. The immunodominant fragments were selected based on propensity scales. The diagnostic antigen was designed using these fragments. Secondary and tertiary structures were predicted and the B-cell epitopes were mapped on the surface of built model. The synthetic DNA coding antigen was sub-cloned into pGS21a expression vector. SDS-PAGE analysis showed that glutathione fused antigen was highly expressed in E. coli BL21 (DE3) cells. The recombinant antigen was purified by nickel affinity chromatography. ELISA results showed that soluble antigen could specifically react with the HTLV-I and HBV infected sera. This specific antigen could be used as suitable agent for antibody-antigen based screening tests and can help clinicians in order to perform quick and precise screening of the HBV and HTLV-I infections.

Strongyloidiasis in immigrants in Southern Spain

OBJECTIVE: To analyse clinical and epidemiological characteristics of immigrant patients diagnosed with strongyloidiasis in our area. METHODS: An analyse was performed on patients with strongyloidiasis seen in the Tropical Medicine Unit of the "Hospital de Poniente" in Almeria (Spain), from April 2004 to May 2012. RESULTS: A total of 320 patients were diagnosed with Strongyloides stercoralis infection, and 284 out of 314 patients (90.4%) had a positive specific serology. Forty-two percent of the patients reported symptoms and 45% had eosinophilia. The serological results were monitored in some of the patients, confirming a loss of antibodies in all 20 patients studied. CONCLUSIONS: Strongyloidiasis is a parasitic disease increasingly diagnosed in developed countries due to increased migratory flows from endemic areas. Often being asymptomatic, its diagnosis and treatment may prevent fatal outcomes, especially in immunocompromised patients

OBJETIVO: Analizar las características clínicas y epidemiológicas de los pacientes inmigrantes diagnosticados de strongyloidiasis en nuestra área. MÉTODOS: Se analizaron retrospectivamente los pacientes con strongyloidiasis que acudieron a la Unidad de Medicina Tropical del Hospital de Poniente de Almería (España), entre abril de 2004 mayo de 2012. RESULTADOS: 320 pacientes han sido diagnosticados con infección por S. stercoralis, 284/314 pacientes (90,4%) tenían una serología específica positiva. 42,3% de los pacientes presentaron síntomas y el 45% de los pacientes tenían eosinofilia. La monitorización del tratamiento confirmó la pérdida de anticuerpos en los 20 pacientes estudiados. CONCLUSIONES: La estrongiloidiasis es una parasitosis diagnosticada cada vez con más frecuencia en países desarrollados debido al aumento de los movimientos migratorios procedentes de zonas endémicas. Siendo a menudo asintomática, su diagnóstico y tratamiento pueden prevenir resultados fatales

[Relevance of safety measures to avoid HTLV transmission by transfusion in 2014]. / Pertinence des mesures sécuritaires transfusionnelles vis-à-vis du HTLV en 2014.

In high-income countries, the safety of blood transfusion related to viruses has reached a very high level, especially thanks to the implementation of multiple measures aimed at reducing the transfusion risk. The cost-effectiveness of these preventive measures is frequently discussed due to global financial resources, which are more and more limited. Hence, the revision of safety strategies is a key issue, especially when these strategies are redundant, as those implemented to avoid Human T-cell Lymphotropic Virus (HTLV) transmission, which are based on both antibodies screening and leucoreduction of blood products. The residual risk of the transmission of HTLV by transfusion has been recently estimated at 1 in 20 million donations (2010-2012) in France (excluding overseas territories). This estimation did not take into account the leucoreduction, which appears to be a very efficient preventive measure as the virus is strictly intra-cellular. To help decision-making, we have evaluated some parameters related to HTLV blood transmission. Firstly, the probability that an incident occurring during the leucoreduction process affects a HTLV-positive blood donation has been estimated at 1 in 178 million. Estimation of clinical consequences of HTLV-positive transfusions would affect 1 to 2 transfused-patients without leucoreduction, and one recipient every 192 years in case of 10% failures of the filtration method. Obviously, despite a risk, which appears to be controlled, HTLV screening will be disputed as soon as the efficiency of leucoreduction to totally prevent virus blood transmission will be proven and when pathogen inactivation methods are generalized to all blood cellular products.

Adult T-cell leukemia-lymphoma associated with follicular mucinosis.

Follicular mucinosis is frequently associated with follicular mycosis fungoides, but its association with adult T-cell leukemia-lymphoma (ATLL) is extremely rare. We report a case of a 50-year-old female patient with a history of ATLL, after multiple treatments, with residual/recurrent skin tumors in the forehead and legs. Biopsy of a skin tumor from the forehead revealed a perifollicular and intrafollicular atypical lymphoid infiltrate with abundant mucin deposition. Immunohistochemical stains showed that the atypical cells were positive for CD3, CD4, and CD25. Reverse transcription polymerase chain reaction performed on the tissue sections confirmed the presence of human T-cell leukemia virus in the biopsies of skin tumors. To our knowledge, this is only the third reported case of a follicular mucinosis in the setting of ATLL.

Human T-lymphotropic virus laboratory testing of maternal blood at time of cord blood donations and clinical implications.

BACKGROUND: In the United States, blood products are tested for infectious diseases including human T-lymphotropic virus (HTLV)-I/II. Positive results of maternal blood samples at the time of cord blood (CB) donation must be reported to mother and physician. Tests for HTLV have a high false-positive rate. This is problematic because there is no prenatal testing of the mother. STUDY DESIGN AND METHODS: This study involves 119,769 maternal blood samples at time of CB donation and evaluates positive results for HTLV in screening tests, supplemental immunoassays, and nucleic acid tests (NATs). Infectious disease markers (IDMs) and maternal health histories of HTLV-positive and -negative mothers were compared. RESULTS: Of 119,769 mothers donating CB, 545 tested positive with the screening test, 33 were positive with the supplemental tests, and two were positive with NAT. When indeterminate results were excluded from the supplemental test only six were positive. Eight of 34 mothers with positive or indeterminate supplemental test results had received intravenous immunoglobulin. There were no significant differences between HTLV-positive and -negative mothers with regard to the incidence of other IDMs. CONCLUSIONS: Testing maternal blood for HTLV is problematic for CB banks, obstetricians, and mothers because of the high false-positive rate. CB banks need rapid turnaround time and supplemental testing. If results on the latter are positive the obstetrician should be notified, educated, do follow-up testing, and counseling. Indeterminate results on supplemental tests are most likely false positives. We recommend that mothers with positive or indeterminate supplemental test results have follow-up NAT.

Infectious disease screening of blood specimens collected post-mortem provides comparable results to pre-mortem specimens.

Serology assays for standard screening are optimised for use with sera collected from living adults and children. Because of potential changes in the vascular compartments after death, methods used for screening sera from cadaveric organ donors need to be validated before testing these specimens. Serum was separated from blood collected from cadaveric donors within 24 h of death and biochemical parameters measured to detect dilution of protein and haemolysis. In order to demonstrate if any inhibitors that might interfere with the assays were present, pre and post-mortem specimens were spiked with aliquots of human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), human T-cell Lymphotropic Virus (HTLV) and T. pallidum-positive sera. Comparison of serum from living subjects with serum obtained post-mortem showed that while the concentration of total protein decreased, concentrations of albumin, immunoglobulin G (IgG) and immunoglobulin M (IgM) remained unchanged. The degree of haemolysis, as measured by free haemoglobin, was within the limits accepted for the Architect analyser. Spiking of pre- and post-mortem specimens with aliquots of HIV, HCV, HBV, HTLV and T. pallidum-positive sera showed no statistical difference in the signal between pre-mortem and post-mortem results when tested on the Abbott Architect analyser. Positive results were obtained in each of a further nine subjects who had tested positive for HIV (n=1), HCV (n=8), HBV (n=1) on pre-mortem serological testing. These findings suggest that the sensitivity of the Abbott Architect serological screening tests is not significantly affected in specimens collected within 24 h of the cessation of life.

Neurological manifestations of coinfection with HIV and human T-lymphotropic virus type 1.

HIV-individuals are at risk for human T-lymphotropic virus (HTLV) coinfection and neurological diseases. Little is known about the impact of HAART among coinfected patients. In this study, 47 out of 428 HIV individuals were coinfected with HTLV (10.9%). Coinfection was an independent variable associated with neurological outcome (odds ratio 8.73). Coinfection was associated with myelopathy [chi square (X(2)) = 93, P < 0.001], peripheral neuropathy (X(2) = 6.5, P = 0.01), and hepatitis C virus infection (X(2) = 36.5, P < 0.001). HAART did not appear to protect against neurological diseases and had no impact on HTLV proviral load.

High prevalence of HTLV-I infection in Mashhad, Northeast Iran: a population-based seroepidemiology survey.

BACKGROUND: Mashhad, in the northeast of Iran has been suggested as an endemic area for human T cell lymphotropic virus type I (HTLV-I) infection since 1996. OBJECTIVES: We performed a community-based seroepidemiology study to examine the prevalence and risk factors for HTLV-I infection in the city of Mashhad. STUDY DESIGN: Between May and September 2009, overall 1678 subjects from all the 12 geographical area of Mashhad were selected randomly by multistage cluster sampling for HTLV antibody. The study population included 763 males and 915 females, with the mean age of 29.1 ± 18.5 years. 1654 serum samples were assessed for HTLV antibody using ELISA and reactive samples were confirmed by Western blot and PCR. RESULTS: The overall prevalence of HTLV-I infection in whole population was 2.12% (95% CI, 1.48-2.93) with no significant difference between males and females (p = 0.093) and the prevalence of HTLV-II seropositivity was 0.12% (95% CI, 0.02-0.44). The HTLV-I Infection was associated with age (p<0.001), marital status (p<0.001), education (p = 0.047), and history of blood transfusion (p = 0.009), surgery (p<0.001), traditional cupping (p = 0.002), and hospitalization (p = 0.004). In logistic regression analysis, age was the only variable that had a significant relation with the infection (p = 0.006, OR = 4.33). CONCLUSIONS: Our results demonstrated that Mashhad still remains an endemic area for HTLV-I infection despite routine blood screening. Thus, further strategies are needed for prevention of the virus transmission in whole population.

Prognosis of HTLV-1 positive renal transplant recipients in Iran.

The human T lymphocyte virus-1 (HTLV-1) is the responsible pathogen for diseases such as HTLV-1 associated myelopathy (HAM) and adult T-cell leukemia (ATL). Mashhad, in northeast Iran, with high instances of this infection, has a noticeable number of infected renal failure patients. Since immunosuppressive drugs might decrease the latency period of HTLV-1 or increase its complications, the question arises whether HTLV-1 positive renal failure patients are suitable candidates for kidney transplants. To answer this, HTLV-1 positive recipients were evaluated in our study. Patients were divided into two groups. First group consisted of patients at the Imam Reza Hospital dialysis center. Second group had 20 kidney transplantation recipients consisting of ten infected and ten uninfected recipients as control from Imam Reza. Medical history of these patients was recorded and evaluated. The follow-up periods were between one and six years. Among them, 3.8% of patients undergoing dialysis were infected. The most important fact resulting from this study is that none of the infected recipients suffered from HAM or ATL during the follow-up period. In addition, it did not show any significant difference in the incidence of post-transplant complications between the infected and non-infected groups. Our study indicates that HTLV-1 positive patients may undergo kidney transplant without fear of increased incidence of side effects than those found in uninfected recipients. Because of short-term follow-up, probable long latency period of the virus, and the limited number of infected recipients, further work on this issue would be prudent.

Antibodies to the envelope glycoprotein of human T cell leukemia virus type 1 robustly activate cell-mediated cytotoxic responses and directly neutralize viral infectivity at multiple steps of the entry process.

Infection of human cells by human T cell leukemia virus type 1 (HTLV-1) is mediated by the viral envelope glycoproteins. The gp46 surface glycoprotein binds to cell surface receptors, including heparan sulfate proteoglycans, neuropilin 1, and glucose transporter 1, allowing the transmembrane glycoprotein to initiate fusion of the viral and cellular membranes. The envelope glycoproteins are recognized by neutralizing Abs and CTL following a protective immune response, and therefore, represent attractive components for a HTLV-1 vaccine. To begin to explore the immunological properties of potential envelope-based subunit vaccine candidates, we have used a soluble recombinant surface glycoprotein (gp46, SU) fused to the Fc region of human IgG (sRgp46-Fc) as an immunogen to vaccinate mice. The recombinant SU protein is highly immunogenic and induces high titer Ab responses, facilitating selection of hybridomas that secrete mAbs targeting SU. Many of these mAbs recognize envelope displayed on the surface of HTLV-1-infected cells and virions and several of the mAbs robustly antagonize envelope-mediated membrane fusion and neutralize pseudovirus infectivity. The most potently neutralizing mAbs recognize the N-terminal receptor-binding domain of SU, though there is considerable variation in neutralizing proficiency of the receptor-binding domain-targeted mAbs. By contrast, Abs targeting the C-terminal domain of SU tend to lack robust neutralizing activity. Importantly, we find that both neutralizing and poorly neutralizing Abs strongly stimulate neutrophil-mediated cytotoxic responses to HTLV-1-infected cells. Our data demonstrate that recombinant forms of SU possess immunological features that are of significant utility to subunit vaccine design.

Risk of bronchioloalveolar carcinoma in patients with human T-cell lymphotropic virus type 1 (HTLV-I): case-control study results.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-I) causes not only adult T-cell leukemia (ATL) but also HTLV-I associated T-cell bronchioloalveolitis, which is often chronic and subclinical. We have experienced eight HTVL-I carriers with bronchioloalveolar carcinoma, which is known to arise from bronchioloalveolar pneumocytes. This case-control study clarified the risk of bronchioloalveolar carcinoma in HTLV-I carriers. MATERIALS AND METHODS: During the past four years, 212 lung cancer patients were examined for serum anti-HTLV-I antibody. They underwent surgical treatment for lung cancer at Kumamoto University Hospital. Of these, 8 (4%) were HTLV-I carriers. As controls for this case-control study, we selected 24 HTLV-I negative-lung cancer patients (1:3 case-control ratio) matched for sex, age, and smoking status. The distributions of histological types of lung cancer were compared between the case (HTLV-I positive) and control (HTLV-I negative) groups. RESULTS: Histological types of the 8 HTLV-I carriers were bronchioloalveolar carcinoma in 6 patients and adenocarcinoma with bronchioloalveolar carcinoma component in 2. The prevalence of bronchioloalveolar carcinoma in HTLV-I carriers, 6 of 8 (75%), was significantly higher than the 6 of 24 (25%) in HTLV-I negative patients (p = 0.02). The prevalence of bronchioloalveolar carcinoma or adenocarcinoma with bronchioloalveolar carcinoma component in HTLV-I carriers, 8 of 8 (100%), was also significantly higher than the 13 of 24 (54%) in HTLV-I negative patients (p = 0.02). CONCLUSION: HTLV-I might be one risk of bronchioloalveolar carcinoma, probably because of inflammatory and/or immunologic responses involving bronchioloalveolar pneumocytes.

Human T-Lymphotropic virus (HTLV) type I in vivo integration in oral keratinocytes

Although the infection of HTLV-1 to cell components of the mouth have been previously reported, there was not until this report, a detailed study to show the characteristics of such infection. From 14 Tropical Spastic Paraparesis/ HTLV-1-Associated Myelopathy (HAM/TSP) patients and 11 asymptomatic carrier individuals (AC) coming from HTLV-1 endemic areas of southwest Pacific of Colombia, infected oral mucosa cells were primary cultured during five days. These cell cultures were immunophenotyped by dual color fluorescence cell assortment using different lymphocyte CD markers and also were immunohistochemically processed using a polyclonal anti-keratin antibody. Five days old primary cultures were characterized as oral keratinocytes, whose phenotype was CD3- /CD4-/CD8-/CD19-/CD14-/CD45-/A575-keratin+. From DNA extracted of primary cultures LTR, pol, env and tax HTLV-1 proviral DNA regions were differentially amplified by PCR showing proviral integration. Using poly A+ RNA obtained of these primary cultures, we amplify by RT-PCR cDNA of tax and pol in 57.14 percent (8/14) HAM/TSP patients and 27.28 percent (3/11) AC. Tax and pol poly A+ RNA were expressed only in those sIgA positive subjects. Our results showed that proviral integration and viral gene expression in oral keratinocytes are associated with a HTLV-1 specific local mucosal immune response only in those HTLV-1 infected individuals with detectable levels of sIgA in their oral fluids. Altogether the results gave strong evidence that oral mucosa infection would be parte of the systemic spreading of HTLV-1 infection.