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.

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.

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.

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.

Current management of adult T-cell leukemia/lymphoma.

When oncologists diagnose patients suspected of lymphoid malignancy, it is important to consider the possibility of adult T-cell leukemia/lymphoma (ATL) with a routine check for serum human T-cell lymphotropic virus type 1 (HTLV-1) antibody. The following points are essential for the diagnosis of ATL: (1) cytologically or histologically proven peripheral T-cell malignancy, and (2) positivity for anti-HTLV-1 antibody. When a patient is diagnosed with ATL, it is important to make an accurate diagnosis of clinical subtype in order to make appropriate treatment decisions. For patients with smoldering or chronic type ATL, close observation with careful monitoring for opportunistic infections is recommended. For patients with the acute or lymphoma type requiring therapy, enrollment in a clinical trial is recommended. When there is no active trial or the patient is ineligible for a trial, we recommend intensive chemotherapy used for aggressive non-Hodgkin lymphoma such as the LSG15 regimen (VCAP-AMP-VECP) based on a recent phase III study. Because most patients with ATL are not curable with current chemotherapy regimens, it is reasonable to consider the applicability of allogeneic stem cell transplantation inpatients who show responses to chemotherapy. For relapsed or refractory patients, enrollment in a new-agent trial should be considered in addition to stem cell transplantation.

Increased frequency of CD4+T cells expressing fractalkine receptor CX3CR1 in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its AIDS susceptible polymorphisms are not associated with the disease.

To investigate whether fractalkine receptor CX3CR1 polymorphisms that have been associated with rapid progression to AIDS among HIV-1 positive individuals also affects the risk of human T cell lymphotropic virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP), we compared the allele frequencies of V249I and T280M between 233 HAM/TSP patients and 213 HTLV-1 seropositive asymptomatic carriers (HCs). Although the frequency and absolute number of peripheral blood CX3CR1+CD4+T cells were significantly increased in HAM/TSP patients compared to HCs and uninfected controls independent of HTLV-1 trans-activator protein Tax, we could not observe any association between the two polymorphisms and the risk of HAM/TSP in our cohort.

Adult T-cell leukemia/lymphoma in an adolescent presenting with skin lesions.

Adult T-cell leukemia/lymphoma is a T-cell malignancy caused by the human T-cell lymphotropic virus-I. Adult T-cell leukemia/lymphoma is primarily a disease of adults due to the long latency period between initial infection and development of leukemia. We present a case of acute adult T-cell leukemia/lymphoma in an adolescent. Skin lesions had appeared 3 years earlier and were the initial sign of human T-cell lymphotropic virus-I infection and T-cell malignancy. Her disease failed to respond to both intensive chemotherapy and antiviral therapy. Cutaneous lesions are sometimes the initial sign of adult T-cell leukemia/lymphoma and early recognition is imperative.

Association between maternal antibodies to the external envelope glycoprotein and vertical transmission of human T-lymphotropic virus type I. Maternal anti-env antibodies correlate with protection in non-breast-fed children.

Vertical transmission of human T-lymphotropic virus type I (HTLV-I) depends primarily on breast-feeding; substitution of bottle-feeding has reduced the transmission rate from 20% in breast-fed children to 3% among bottle-fed. To determine the correlates of transmission for long breast-feeding (> or = 6 mo), short breast-feeding (< 6 mo), and bottle-feeding mothers, the antibody titers of transmitter (T) mothers and non-transmitter (nT) mothers were analyzed by using synthetic and recombinant epitopes representing the immunodominant epitopes of gag (Gag1a, r24), env (Env1/5, MTA1, RE3), and tax (Tax8/22-24) proteins. Seroreactivity to gag and tax epitopes was not significantly different except for anti-r24 antibody titer, which was significantly higher among T-mothers (geometric mean 134) when compared with nT-mothers (62) in the long-feeding group (P < 0.001). Profiles of antibody titers against env epitopes were different. Within the long-feeding group, Env1/5, MTA1, and RE3 titers were significantly higher among T-mothers (258, 1,476, and 738, respectively) when compared with nT-mothers (106, 279, and 320, respectively) (P < 0.01 for all three epitopes). In contrast, within the bottle-feeding group, antibody titers to Env1/5 (269) and RE3 (418) among nT-mothers were significantly higher than those among T-mothers (80 and 113, respectively) (P < 0.01). These data confirm that high-titered anti-HTLV-I antibodies in the long-feeding group correlate with milk-borne transmission of HTLV-I and, more importantly, imply that maternal anti-env antibodies may reduce the risk of non-milkborne infection.

Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States.

BACKGROUND: Tissue-banking organizations in the United States have introduced various review and testing procedures to reduce the risk of the transmission of viral infections from tissue grafts. We estimated the current probability of undetected viremia with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-lymphotropic virus (HTLV) among tissue donors. METHODS: Rates of prevalence of hepatitis B surface antigen (HBsAg) and antibodies against HIV (anti-HIV), HCV (anti-HCV), and HTLV (anti-HTLV) were determined among 11,391 donors to five tissue banks in the United States. The data were compared with those of first-time blood donors in order to generate estimated incidence rates among tissue donors. The probability of viremia undetected by screening at the time of tissue donation was estimated on the basis of the incidence estimates and the window periods for these infections. RESULTS: The prevalence of confirmed positive tests among tissue donors was 0.093 percent for anti-HIV, 0.229 percent for HBsAg, 1.091 percent for anti-HCV, and 0.068 percent for anti-HTLV. The incidence rates were estimated to be 30.118, 18.325, 12.380, and 5.586 per 100,000 person-years, respectively. The estimated probability of viremia at the time of donation was 1 in 55,000, 1 in 34,000, 1 in 42,000, and 1 in 128,000, respectively. CONCLUSIONS: The prevalence rates of HBV, HCV, HIV, and HTLV infections are lower among tissue donors than in the general population. However, the estimated probability of undetected viremia at the time of tissue donation is higher among tissue donors than among first-time blood donors. The addition of nucleic acid-amplification testing to the screening of tissue donors should reduce the risk of these infections among recipients of donated tissues.

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.

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.

Antibodies to HTLV-I p24 in African and Portuguese populations.

Using a radioimmunoassay to detect HTLV-I protein antibodies of molecular weight 24,000, we screened populations from Algeria (140 subjects), Tunisia (442), Mali (69), Senegal (415), Uganda (135), the Central African Republic (77), the Congo (360), and Madagascar (193). Only four subjects were positive (1 from Senegal, 1 from Uganda, 2 from the Congo). This is a much lower figure than that found by others in Africa by the enzyme-linked immunosorbent assay technique. In addition, 319 Portuguese blood donors (46 of whom have lived in Angola or Mozambique) were screened using the same radioimmunoassay. All were negative.

Seroepidemiology of human T-cell lymphotropic virus type I infection in Taiwan.

The epidemiological characteristics of human T-cell lymphotropic virus type I infection in Taiwan have been explored by an island-wide community-based survey, which was carried out among residents in 19 townships and metropolitan precincts randomly selected through stratified sampling. Serum specimens of 7278 healthy subjects were screened by enzyme-linked immunosorbent assay and confirmed by Western blot method. A total of 103 subjects showed positive or weak reactions by enzyme-linked immunosorbent assay, but only 35 of them were confirmed to be positive by Western blot analysis. The anti-human T-cell lymphotropic virus type I antibody positive rate was 4.81/1000. The seropositive rate increased with age in both males and females, and females had a greater seropositive rate than males for all the age groups. Aborigines and Hakka Taiwanese had higher seropositive rates than Fukien Taiwanese and Mainland Chinese. Those people with lower educational levels were found to be associated with higher anti-human T-cell lymphotropic virus type I seropositive rates.

Clinical diversity in adult T-cell leukemia-lymphoma.

Adult T-cell leukemia-lymphoma (ATL) is a unique T-cell cancer first described in Japan. We estimate that more than 200 patients a year have been detected in Kyushu. The surface phenotype of ATL cells characterized by monoclonal antibodies is T3+, T4+, T8-, T11+, and Tac+. In all cases the serum is positive for anti-human T-cell leukemia (lymphotropic) virus (HTLV-I) antibodies and the ATL cells contain the proviral DNA of HTLV-I. Variations in the clinical features of atypical cases suggest a division of the spectrum of ATL into five types: acute (prototypic), chronic, smoldering, crisis, and lymphoma. Screening of the sera from healthy adults for presence of the anti-HTLV-I antibodies revealed that 3.6% of healthy individuals in Kumamoto Prefecture, which is located in the middle of Kyushu, were HTLV-I carriers. The percentage of positivity increased with age and was higher in females than in males. It varied from town to town, ranging from 0 to 17.6%. Family studies showed that the routes of natural infection of HTLV-I are from mother to child and also from husband to wife. The third route is blood transfusion. The borderline between the healthy carrier state and smoldering ATL remains unclear. In the endemic areas smoldering ATL is frequently diagnosed in patients with fungus infection of the skin, chronic lymphadenopathy, interstitial pneumonitis, chronic renal failure, and strongyloidiasis. In addition our experiences with a concurrence of lymphoma-type ATL in three sisters and spontaneous remissions in a patient with chronic ATL are cited.

Production of oncogene-specific proteins and human T-cell leukemia (lymphotropic) retrovirus (HTLV-I) envelope protein in bacteria and its potential for use in human cancers and seroepidemiological surveys.

The oncogenes coding for the Harvey murine sarcoma virus p21ras protein as well as those coding for myc, myb, and mht products were fused to the amino-terminal portion of the bacteriophage lambda cII gene on the expression vector pJL6. In addition two regions of the gene for the human T-cell leukemia virus subgroup I (HTLV-I) envelope were expressed in our bacterial system. Each of 11 human sera tested that had been shown to contain antibodies to HTLV-I or -II by an enzyme-linked immunosorbent assay recognized the bacterially synthesized envelope proteins. No reaction was detected when 17 control sera were tested. This system will be useful for large-scale seroepidemiological surveys for HTLV-I and related human retroviruses. The other oncogene products expressed in our bacterial vector system also demonstrated specific immunoreactivities. In addition to this feature the bacterial ras protein was seen to bind guanosine diphosphate and was capable of autophosphorylation. Taken together these data suggest that the proteins produced with high efficiency by the bacterial expression system can be immunologically recognized as antigens and can in part perform some of their associated biochemical functions.

Subunit vaccines against exogenous retroviruses: overview and perspectives.

Vaccines prepared from purified viral envelope complexes are effective against certain animal model tumors induced by exogenous retroviruses. Related viruses have recently been isolated from humans and obviously cause adult T-cell leukemia and the acquired immunodeficiency syndrome. Knowledge accumulated in experiments with subunit vaccines against animal retroviruses could help to develop immunopreventive regimens against human retroviruses.

Seroprevalence and risk factors for human T cell lymphotropic virus type 1 and 2 infection in human immunodeficiency virus-infected patients attending AIDS referral center health units in Londrina and other communities in Paraná, Brazil.

The municipality of Londrina ranks second in the number of AIDS cases in the state of Paraná, Brazil, with the Ministry of Health notified of 1070 cases from 1984 to 2002. The aim of this study was to determine the seroprevalence and risk factors for HTLV-1/2 infection in HIV-infected patients attending the AIDS Reference Center serving Londrina (and surrounding region), Paraná, Brazil. Data concerning sociodemographic conditions and risk factors were collected from 784 HIV-infected patients, using a questionnaire. Blood samples were obtained from 758 of the patients and subjected to serologic screening tests for the determination of HTLV-1/2, as well as hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis. Most patients were white (mean age, 35.9 years); 55.9% were males and 44.1% were females. The most frequent sexually transmitted disease was gonorrhea (28.5%), followed by syphilis (14.3%) and condyloma (12.2%). The major risk factors associated with the acquisition of retroviruses were sexual contact (84.8%) and intravenous drug use (IDU, 11.9%). The overall infection seroprevalence was 6.4% for HTLV-1/2, 37.2% for HBV, 21.0% for HCV, and 24.4% for syphilis. HTLV-1 and HTLV-2 infections were confirmed in 0.8 and 4.9% of patients, respectively. HIV/HTLV-1/2 coinfection was more frequent in IDUs (59.2% of cases) and was strongly associated with HCV (22.60 [95% CI, 10.35-49.35]). A weak association with HBV (2.09 [95% CI, 1.13-3.90]) and no association with syphilis were observed. The results showed that human retroviruses are circulating in southern Brazil, mainly among white people of both genders of low socioeconomic conditions and educational level. Although the sexual route was considered to be the major risk factor for HIV infection, HTLV-1/2 infection was strongly associated with IDU.