Novel insights into human T-lymphotropic virus type-1 (HTLV-1) pathogenesis-host interactions in the manifestation of HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T-lymphotropic virus type-1 (HTLV-1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T-cell leukaemia/lymphoma malignancy and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro-myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV-1-associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV-1-infected individuals (∼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV-1 a natural probe for the study of malignancy and neuro-inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV-1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro-inflammatory propensity of HTLV-1-induced HAM/TSP. Such an emphasis on the virus-host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV-1 therapeutics.

Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Role of Interleukin-17 cytokine family in human T-cell lymphotropic virus type 1 (HTLV-1) infection and associated diseases.

BACKGROUND: Human T-lymphotropic virus (HTLV-1) is a neglected virus with worldwide distribution of over 10 million people and is the cause of two main associated diseases Adult T cell Leukemia-Lymphoma (ATLL), and HTLV-1-associated Myelopathy/Tropical Spastic paraparesis (HAM/TSP). The IL-17 cytokine family plays a crucial role in the host immunity against HTLV-1 and the development of associated disease. A systematic review was conducted to analyze all research reporting on the levels or expression of the IL-17 HTLV-1 infection and associated diseases. METHODS: The literature search was conducted in electronic databases including PubMed/Medline and Web of Sciences until January 31st, 2024, followed by the PRISMA guidelines. RESULTS: Our search revealed 20 eligible articles to be included in our study. The total number of cases studied was 1420, of which 386 were carriers without any symptoms, and were 176 ATLL and 237 HAM/TSP. The IL-17 cytokine family production or mRNA expression was higher in HAM/TSP patients but showed a trend toward reduction in the case of ATLL. CONCLUSIONS: Our results showed that while The IL-17 cytokine family plays a significant role in the immunopathogenesis of disease and clinical status of patients with inflammatory disorders such as HAM/TSP, IL-17 production is diminished and the RORC/IL-17 signaling pathway is downregulated during ATLL. Our data suggest that boosting the RORC/IL-17 signaling pathway in ATLL and using anti-IL-17 agents in HAM/TSP and other HTLV-related inflammatory conditions might benefit patients and improve their outcomes.

Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.

A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.

Immune response to COVID-19 vaccines among people living with human T-cell lymphotropic virus type 1 infection: a retrospective cohort study from Iran.

The effectiveness of COVID-19 vaccination is still unclear in individuals with underlying diseases such as HTLV-1 infection. This retrospective cohort study aimed to evaluate the humoral response of COVID-19 vaccines among people living with HTLV-1 (PLHTLV) in northeastern Iran. From December 2021 to October 2022, eighty-six HTLV-1+ subjects (50 males and 36 females; 47.7 ± 11.2 years) and 90 HTLV-1 seronegative individuals (age- and sex-matched convenient samples) were enrolled. The humoral immune response was evaluated by measuring different COVID-19 Abs in serum samples at least 28 days after receiving 2nd or 3rd doses of COVID-19 vaccines. Throughout all three rounds of immunization, Sinopharm was the most commonly used COVID-19 vaccine across all three immunization rounds. Compared to the HTLV-1- group, a significantly lower frequency of all four Abs activity was observed among PLHTLV:anti-nucleocapsid (66.3% vs 86.7%, p = 0·001), anti-spike (91.9% vs 98.9%, p = 0·027), RBD (90.7% vs 97.8%, p = 0·043), and neutralizing Abs (75.6% vs 95.5%, p < 0·001). Also, the frequency of all Abs in 28 patients with HAM/TSP was higher than that of 58 asymptomatic carriers, although this difference was statistically significant only in the case of anti-spike Abs (p = 0.002). Notably, PLHTLV-vaccinated against COVID-19 demonstrated significantly lower antibody activities, indicating a reduced humoral immune response to COVID-19 vaccines.

XCL1, a serum biomarker in neurological diseases; HTLV-1-associated myelopathy and multiple sclerosis.

The XCL1-XCR1 axis has a potential role in the recruitment of immune cells to the site of inflammation. The present study aimed to examine the relation of XCL1 serum levels with Multiple sclerosis (MS) and HTLV-1-associated myelopathy (HAM), as chronic inflammatory diseases of the central nervous system (CNS). DNA was extracted to evaluate HTLV-1 proviral load (PVL) using real-time PCR. Serum levels of XCL1 was determined by using an ELISA assay. The serum level of XCL1 was significantly higher in patients with HAM than that of asymptomatic carriers (ACs) and healthy controls (HCs) (p < 0.001 and p < 0.0001, respectively) and was also higher in MS patients compared to HCs (p < 0.0001). Moreover, the concentration of XCL1 serum level was significantly different between the ACs and HCs group (p < 0.0001). In conclusion, increased expression of XCL1 might contribute to the migration of autoreactive T cells to the central nervous system and play a critical role in the development and pathogenesis of inflammatory neurological diseases including HAM and MS.

Development and validation of a duplex real-time PCR for the rapid detection and quantitation of HTLV-1.

BACKGROUND: The HTLV-1 prevalence in China varies geographically, while HTLV-2 infection has rarely been found so far. Proviral load is one of the determining factors of pathogenesis and progression of HTLV-1 related diseases. However, neither molecular assays nor commercial kits are available for HTLV-1 diagnosis in China. The objective of the present study was to develop and validate a TaqMan qPCR assay for HTLV-1 proviral load quantification. RESULTS: A plasmid containing both the HTLV-1 of interest and a fragment of the RNase P (RPPH1) gene was constructed and used to establish the standard curves. The assay has a wide dynamic range (2.5 × 108 copies/reaction ~ 25 copies/reaction) and sensitive to 1 copy for HTLV-1 and RPPH1. The limit of detection for Hut102 cell concentration was 0.0218% (95% confidence interval 0.0179-0.0298%). The assay gave coefficient of variation (CV) for both the HTLV-1 and RPPH1 Ct values. All of the HTLV-1 sero-negative samples and MOT cell line (infected with HTLV-2) amplified only the RPPH1 gene by our method, presenting 100% specificity. 85 Samples confirmed positive or indeterminate by LIA were performed by established qPCR assay and WB. 90.0% (27/30) of LIA-HTLV-1-positive, 33% (2/6) of LIA-untypeable and 2% (1/49) of LIA-indeterminate samples were defined as qPCR-positive. The median PVL of LIA-positive samples (n = 27, 1.780 copies/100 cells) was much higher than that of LIA-untypeable and (n = 2, 0.271 copies/100 cells) indeterminate samples (n = 1, 0.017 copies/ 100 cells). Additionally, compared to WB, the duplex qPCR verified more positive samples, demonstrating a better sensitivity. CONCLUSION: The duplex qPCR developed here with high sensitivity, good specificity and reproducibility could accurately and quantitatively detect the HTLV-1 PVLs, which can be used to confirm the initial reactive samples for an improved cost/benefit ratio as well as to monitor the clinical progression and efficacy of therapy in patients with HTLV-1 related disease.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Pentraxin 3, a serum biomarker in human T-cell lymphotropic virus type-1-associated myelopathy patients and asymptomatic carriers.

Human T-cell lymphotropic virus type 1 (HTLV-1) can induce a neuroinflammatory condition that leads to myelopathy. Pentraxin 3 (PTX3) is an acute-phase protein that its plasma concentration increases during inflammation. We aimed to determine whether PTX3 serum level is elevated in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and HTLV-1 asymptomatic carriers (ACs) and evaluate its association with proviral load and clinical features. The serum level of PTX3 was measured using an enzyme-linked immunosorbent assay in 30 HAM patients, 30 HTLV-1 ACs, and 30 healthy controls. Also, the HTLV-1 proviral load was determined via real-time PCR technique. The findings showed that PTX3 serum level was significantly higher in HAM patients than in both asymptomatic carriers and healthy controls (p values < 0.0001). No correlation between PTX3 and the proviral load was observed in HAM patients and asymptomatic carriers (r = - 0.238, p = 0.205 and r = - 0.078, p = 0.681, respectively). The findings showed that there was no significant correlation between PTX3 and motor disability grading (MDG) (r = - 0.155, p = 0.41) nor urinary disturbance score (UDS) (r = - 0.238, p = 0.20). Higher levels of PTX3 are associated with HTLV-1-associated myelopathy compared to asymptomatic carriers. This finding may support the idea that PTX3 has the potential as a diagnostic biomarker.

Evolution of erectile dysfunction in individuals infected with human T-lymphotropic virus 1: a prospective cohort study.

BACKGROUND: Virtually all patients with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have some degree of erectile dysfunction (ED), but ED is also found in a large percentage of HTLV-1 carriers. AIM: To evaluate the evolution of ED in individuals infected with HTLV-1 who were followed for up to 15 years. METHODS: This prospective cohort study included men infected with HTLV-1 who had ED, were aged 18 to 70 years, and were followed from January 2004 to December 2019. We used the International Index of Erectile Function-5 (IIEF-5), the Expanded Disability Status Scale and Osame Motor Disability Scale, and the Overactive Bladder Symptom Score (OABSS) to define and stratify ED, neurologic disability, and bladder dysfunction, respectively. OUTCOMES: Time to development of severe ED was the main outcome. RESULTS: We studied 90 men with ED (mean ± SD age, 52.8 ± 9.78 years). At baseline, 42 were carriers, 16 had probable HAM/TSP, and 32 had definite HAM/TSP. IIEF-5 was highest among carriers and lowest in patients with definite HAM/TSP, whereas OABSS was lowest in carriers and highest in patients with definite HAM/TSP. Median (IQR) follow-up was 8.50 years (3.00-12.00). IIEF-5 fell significantly from baseline to last follow-up among carriers and patients with probable and definite HAM/TSP. There was an inverse correlation between the IIEF-5 and the OABSS at last follow-up (r = -0.62, P < .001). In survival analysis, the time to development of severe ED was significantly shorter in patients with definite HAM/TSP when compared with carriers (P = .001) and those with probable HAM/TSP (P = .014). The presence of definite HAM/TSP at baseline was independently associated with the development of severe ED, after adjustment for baseline age and proviral load (hazard ratio, 6.74; P = .008). CLINICAL IMPLICATIONS: Formal assessment of erectile function should be part of the routine clinical assessment of individuals infected with HTLV-1; worsening erectile function should alert clinicians to the possibility of neurologic deterioration. STRENGTHS AND LIMITATIONS: This is the first prospective cohort study to describe the course of ED in men infected with HTLV-1. The small sample size and absence of seronegative controls are limitations. CONCLUSION: ED is a slowly progressive clinical manifestation of HTLV-1 infection, and the degree of neurologic compromise at baseline is the main predictor of time to progression to severe ED.

A human T-lymphotropic virus-1 carrier who developed progressive multifocal leukoencephalopathy following immunotherapy for sarcoidosis: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disorder of the central nervous system caused by opportunistic infection of the JC virus (JCV). CASE PRESENTATION: A 58-year-old Japanese woman was admitted to our hospital for aphasia. She had a 5-year history of untreated sarcoidosis and was a human T cell lymphotropic virus-1 (HTLV-1) carrier. Serum angiotensin-converting enzyme, soluble interleukin-2 receptor, lysozyme, and calcium levels were elevated. JCV-DNA was not detected in cerebrospinal fluid by PCR testing. Skin biopsy revealed noncaseating granuloma formation. Bilateral multiple nodular lesions were present on chest X-ray. Brain magnetic resonance imaging showed left frontal and temporal lesions without gadolinium enhancement. As we suspected that systemic sarcoidosis had developed into neurosarcoidosis, we started steroid and infliximab administration. After treatment, the chest X-ray and serum abnormalities ameliorated, but the neurological deficits remained. At 1 month after immunotherapy, she developed right hemiparesis. Cerebrospinal fluid was positive for prototype (PML-type) JCV on repeated PCR testing. Brain biopsy revealed demyelinating lesions with macrophage infiltration, atypical astrocytes, and JCV antigen-positive cells. We diagnosed her with PML and started mefloquine, leading to partial remission. CONCLUSIONS: Sarcoidosis and HTLV-1 infection both affect T cell function, especially CD4+ T cells, and may developped the patient's PML. The comorbidity of sarcoidosis, PML, and HTLV-1 infection has not been reported, and this is the world's first report of PML associated with HTLV-1 infection and sarcoidosis.

Trend in seroprevalence of HTLV-1/2 in Taiwanese blood donors-A 10-year follow-up.

OBJECTIVES: This study evaluated the Human T-lymphotropic virus (HTLV) screening policy impact on the HTLV seroprevalence from 2009 to 2018 as well as the differences between administrative districts in terms of prevalence distribution in Taiwan. BACKGROUND: Since February 1996, the Taiwan Blood Services Foundation (TBSF) had conducted HTLV screening of blood donors. The HTLV seroprevalence was 0.032% in 1999. MATERIALS AND METHODS: This cross-sectional study included donors' data collected from blood donation centres across Taiwan from 2009 to 2018. Enzyme immunoassay and Western blot assay were used for screening and confirmation of HTLV infections. In this study, the researchers calculated the trends in the HTLV rates of first-time and repeat donors across time as well as the HTLV prevalence distribution across the 22 administrative districts of Taiwan. RESULTS: Amongst 17 977 429 employed blood donations, 739 HTLV-seropositive donations (4.11 per 100 000 donations) were identified. The HTLV-positive donors were aged between 17 and 64 years, with a median age of 49 years. The overall seropositivity rates of first-time and repeat donors were 34.36/100 000 and 1.27/100 000. HTLV seroprevalence in first-time blood donors significantly decreased by 57% (crude odds ratio [95% confidence interval] (crude OR [95% CI]) = 0.43 [0.28-0.64]) within 10 years. A slight decline was also identified in repeat donors (crude OR [95% CI] = 0.73 [0.4-1.32]). Donors from different districts showed significantly varied prevalence. Most districts with high prevalence are situated in eastern Taiwan, for both donation types. Older blood donors were more likely to be infected with HTLV than younger ones in first time and repeat donors. Middle age donors (50-65 years) had an 18.47-39.65 greater risk than those aged <20 years. Significant higher risk of female was observed in both donation types. Amongst different age groups, first-time female donors increase 1.31-1.88 times infection risk and female in repeat donor group had 1.55-3.43 times greater risk. CONCLUSION: Over years of implementation of the HTLV blood donor screening policy by the TBSF, the HTLV seroprevalence of first-time donors has decreased consistently. Moreover, the HTLV seroprevalence of repeat donors has dropped considerably. This implies that the screening policy provides continued benefit. Females and older blood donors were more likely infected with HTLV than males and younger blood donors. The influence of age on infection was greater amongst first-time donors than amongst repeat donors. Therefore, appropriate measures should be taken to ensure public safety.

A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier. CASE PRESENTATION: A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of "decoy cells". Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy. CONCLUSIONS: BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.

Cerebral and spinal cord changes observed through magnetic resonance imaging in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis: a systematic review.

To verify brain and spinal changes using magnetic resonance imaging in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. This was a systematic review. The descriptors used were tropical spastic paraparesis and magnetic resonance image. The keyword HTLV-1-associated myelopathy was also used. Twenty-three articles were included: 16 detected brain changes and 18 detected spinal changes. White matter lesions were the most frequent finding in the brain. Brain injuries were most frequently identified in the periventricular region, in the subcortical region, in the centrum semiovale, in the brain stem, and corpus callosum. Atrophy was the most frequent finding of the spinal cord, affecting the thoracic and cervical regions, and was associated with a longer evolution of myelopathy. White matter lesions in these regions were also observed. Cortical white matter lesions and thoracic spinal cord atrophy were the most frequently reported changes in patients with HTLV-1-associated myelopathy.

Human T-lymphotropic virus in Irish blood donors: Impact on future testing strategy.

AIM: A risk-based approach to the testing of blood donations for Human T-Lymphotropic Virus (HTLV) should include an assessment of blood donation seroepidemiology. The objectives of the present study were to determine the proportion of HTLV positive units in Irish blood donations, and subsequently, to estimate the current risk of transfusion transmitted HTLV (TT-HTLV). METHODS: Over 3 million donations screened between 1996 and 2020, were included in the study (n = 3,666,253). Factors considered in the assessment of TT-HTLV risk included: (I) HTLV seropositivity, (ii) probability of a leucodepletion failure, and (iii) the HTLV testing strategy. RESULTS: Six HTLV positive donations were detected throughout the study period, all of them in previously unscreened blood donors (0.000164%; n = 6/3,666,253), 3 of whom had donated prior to the introduction of HLTV antibody testing. On average 0.11% of manufactured blood components assessed, failed to satisfy the leucodepletion quality assurance criteria of less than 1 × 106 cells/unit. In using these values to model the risk of TT-HTLV, it was shown that the combination of leucodepletion with either universal screening of all = donors, or selective testing of first-time donors, a possible HTLV transfusion transmitted infection would be prevented every 468-3776 years. CONCLUSIONS: This is the first report on the proportion of HTLV positive in Irish blood donations (1996-2020) and will be used to inform blood donation screening policy in Ireland. Evidence is provided for recommending a selective HTLV donor screening algorithm in Ireland that is accompanied by a robust framework for continued surveillance of leucodepletion failure rate.

Association of the rs4143815 polymorphism of PDL1 gene with HTLV-1 infection and proviral load in asymptomatic blood donors in northeast Iran.

It is obvious that genetic differences, including mutations and polymorphisms, can play an important role in viral infections. In this case-control study, which included 81 human T-cell leukemia virus type 1 (HTLV-1) asymptomatic carriers (AC) and 162 healthy controls (HC), the rs4143815 polymorphism of PDL1 gene was investigated. This polymorphism is the site of miR-570 binding and it can influence immune system responses. The rs4143815 polymorphism was evaluated by allele-specific polymerase chain reaction (AS-PCR) and the proviral load levels by quantitative real-time PCR (q PCR). The results demonstrated that the C allele (P = 0.027) and the CC genotype (P = 0.031) of rs4143815 polymorphism was significantly higher in the AC group than in the HC group, also the proviral load in the AC group with the C allele (P = 0.020) was significantly higher. Thus, the rs4143815 polymorphism can play a vital role in HTLV-1 infection.

HTLV-1 oncovirus-host interactions: From entry to the manifestation of associated diseases.

Human T lymphotropic virus type-1 (HTLV-1) is a well-known human oncovirus, associated with two life-threatening diseases, adult T cell leukaemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The study of this oncogenic virus is significant from two different aspects. First, HTLV-1 can be considered as a neglected public health problem, which may spread slowly worldwide. Second, the incidence of HTLV-1 associated diseases due to oncogenic effects and deterioration of the immune system towards autoimmune diseases are not fully understood. Furthermore, knowledge about viral routes of transmission is important for considering potential interventions, treatments or vaccines in endemic regions. In this review, novel characteristics of HTLV-1, such as the unusual infectivity of virions through the virological synapse, are discussed in the context of the HTLV-1 associated diseases (ATL and HAM/TSP).

Seroprevalence of human T-lymphotropic virus infection among blood donors in China: a first nationwide survey.

BACKGROUND: So far, the prevalence of human T-lymphotropic virus (HTLV) type 1 and 2 in some highly populated countries such as China is still unknown. In this study, a multi-center nationwide serological survey was designed and performed, to reveal the seroprevalence of HTLV infection among Chinese blood donors. RESULTS: Among 8,411,469 blood donors from 155 blood establishments, 435 were finally confirmed as HTLV carriers. The prevalence of HTLV infection in China varied in different provinces: Fujian had the highest prevalence of 36.240/100,000 (95% CI 31.990-41.050) and eleven provinces did not find HTLV-seropositive donors in the three years. no HTLV-2 infection was found. The overall prevalence of HTLV-1 in China decreased from 2016 to 2018. Female was identified as an independent risk factor of HTLV infection in China. Besides, seroconversion was observed in two of seven seroindeterminate donors 85 and 250 days after their last donation, respectively. CONCLUSIONS: The seroprevalence of HTLV infection in most areas of China among blood donors is quite low, but it varies significantly in different geographic areas. Screening anti-HTLV-1/2 antibody and follow-up of serointederminate donors are essential to ensure blood safety especially in areas where we have found HTLV infected donors.

First molecular epidemiological study of hepatitis B and D in individuals infected with human T-lymphotropic virus 1/2 from Argentina.

Human T-lymphotropic virus 1/2 (HTLV-1/2), hepatitis B virus (HBV), and hepatitis D virus (HDV) share transmission routes. Argentina shows low prevalence of HTLV-1/2, HBV, and HDV infections; however, this situation may vary according to the geographic region and group studied. The aim of this study was to estimate the prevalence of HBV and HDV infections and detect both viral genotypes in HTLV-1/2 individuals from Argentina. A total of 202 HTLV-1/2 confirmed samples (blood donors [BD] and individuals with risk factors for HTLV-1/2 [RF]) were tested for HBsAg and total anti-HBc by enzyme-linked immunosorbent assay. All reactive samples for some HBV markers were analyzed for HBV DNA characterization and HDV serological and molecular analysis. Total prevalence was 1.5% for HBsAg and 6.4% for anti-HBc. Prevalence was 23.1% for anti-HDV in all HBV-reactive samples. No significant difference was observed for HBV and HDV prevalence within HTLV subtypes. The population study showed that prevalence of anti-HBc was higher in the RF than in the BD population, with no significant differences between them. The HBsAg marker and anti-HDV were only found in RF, showing significant differences when compared to BD. Regarding molecular detection, one sample amplified for HBV DNA and none for HDV RNA. HBV sequence was classified as subgenotype F1b. New and updated background on serological markers of HBV and HDV infection in patients with HTLV-1/2 was provided.

Adult T-Cell Leukemia: a Comprehensive Overview on Current and Promising Treatment Modalities.

PURPOSE OF THE REVIEW: Adult T-cell leukemia (ATL) is an aggressive chemo-resistant malignancy secondary to HTLV-1 retrovirus. Prognosis of ATL remains dismal. Herein, we emphasized on the current ATL treatment modalities and their drawbacks, and opened up on promising targeted therapies with special focus on the HTLV-1 regulatory proteins Tax and HBZ. RECENT FINDINGS: Indolent ATL and a fraction of acute ATL exhibit long-term survival following antiviral treatment with zidovudine and interferon-alpha. Monoclonal antibodies such as mogamulizumab improved response rates, but with little effect on survival. Allogeneic hematopoietic cell transplantation results in long-term survival in one third of transplanted patients, alas only few patients are transplanted. Salvage therapy with lenalidomide in relapsed/refractory patients leads to prolonged survival in some of them. ATL remains an unmet medical need. Targeted therapies focusing on the HTLV-1 viral replication and/or viral regulatory proteins, as well as on the host antiviral immunity, represent a promising approach for the treatment of ATL.