Human T-lymphotropic Virus Type 1 Infection Research Articles

Neurological aspects of HTLV-1 infection: symptoms in apparently asymptomatic carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP.This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.

Impaired humoral immunity following COVID-19 vaccination in HTLV-1 carriers

BackgroundWhether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown.MethodsTo investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors.ResultsWe analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers.ConclusionsThe humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.

Genetic typing and intrafamilial transmission of human T-lymphotropic virus type 1 in non-endemic areas of China.

The origin and intrafamilial transmission of Human T-Lymphotropic Virus Type 1 (HTLV-1) in non-endemic populations such as China is still unknown. In this study, donors from blood banks/centers in China (including 28 provinces and Shenzhen city) during 2019 and 2021 were screened for HTLV-1/2 antibody, and all the reactive samples were tested using a line immunoassay (LIA) and quantitative polymerase chain reaction (qPCR). Samples that can be detected using qPCR were amplified and sequenced for the long terminal repeat (LTR) region. The positive donors were contacted to identify their relatives. As a result, 4,451,883 blood donors were totally tested, and 50 of them were confirmed to be HTLV-1/2 positive. Viral LTR sequences genotyped from 26 HTLV-1 carriers demonstrated that all had the HTLV-1a genotype, of which Transcontinental and Japanese subgroups accounted for half each. There were 17 family members of 11 index donors detected, and the HTLV-1 infection rate in the spouses of male index donors (83.3%, 5/6) was significantly higher than that in the husbands of female index donors (0.0%, 0/4). However, 7 children of HTLV-1 positive women were tested and found negative. Therefore, our findings indicated that HTLV-1 is spreading silently from high-endemic to low-endemic areas in China. To prevent further HTLV-1/2 transmission, an efficient HTLV-1/2 screening strategy and counseling of the virus carriers are essential.

Momordica charantia phytoconstituents can inhibit human T-lymphotropic virus type-1 (HTLV-1) infectivity in vitro and in vivo.

There is an urgent need to find an effective therapy for life-threatening HTLV-1-associated diseases. Bitter melon (Momordica charantia) is considered a traditional herb with antiviral and anticancer properties and was tested in this study on HTLV-1 infectivity. GC-MS analyzed the alcoholic extract. In vitro assay was carried out using transfection of HUVEC cells by HTLV-1-MT2 cell line. The cells were exposed to alcoholic and aqueous extracts at 5,10, and 20µg/mL concentrations. In vivo, mice were divided into four groups. Three groups were treated with HTLV-1-MT-2 cells as test groups and positive control, and PBS as the negative control group in the presence and absence of M. charantia extracts. Peripheral blood mononuclear cells (PBMCs), mesenteric lymph nodes (MLNs), and splenocytes were collected for HTLV-1-proviral load (PVL) assessment, TaqMan-qPCR. The GC-MS analysis revealed 36 components in M. charantia. The studies showed significant reductions in HTLV-1-PVL in the presence of extract in the HUVEC-treated groups (P = 0.001). Furthermore, the inhibitory effects of extracts on HTLV-1 infected mice showed significant differences in HTLV-1-PVL among M. charantia treated groups with untreated (P = 0.001). The T-cells in MLNs were significantly more susceptible to HTLV-1 than others (P = 0.001). There were significant differences among HTLV-1-infected cells in MLNs and splenocytes (P = 0.001 and 0.046, respectively). Also, aqueous and alcoholic extract-treated groups significantly affected HTLV-1-infected PBMCs (P = 0.002 and 0.009, respectively). M. charantia may have effective antiviral properties. The substantial compound of M. charantia could have inhibitory effects on the proliferation and transmission of HTLV-1 oncovirus.

Co-infection of high-risk Human papillomavirus and Human T-lymphotropic virus-1 among women living with HIV on antiretroviral therapy at a tertiary hospital in Kenya

BackgroundGlobally, 15% of reported cancers are virus-associated. Cancer-causing viruses include high-risk Human papillomavirus (HR-HPV), the causative agent of cervical cancer, and Human T-lymphotropic virus type-1 (HTLV-1), the causative agent of adult T-cell leukemia (ATL). HTLV-1 infection may enhance susceptibility to acquiring HR-HPV infections due to its retrovirus properties, resulting in increased cervical abnormalities among women living with HIV (WLHIV). In Kenya, there is a paucity of data on the burden of HR-HPV/HTLV-1 co-infection among WLHIV. We determined the prevalence of HR-HPV and HTLV-1 co-infection among WLHIV on antiretroviral therapy (ART) at Kenya’s national referral hospital, Kenyatta National Hospital (KNH).MethodologyWe conducted a cross-sectional study among WLHIV on ART attending KNH’s HIV care clinic. Study nurses collected a cervical sample with a cytobrush for HPV genotyping using Gene Xpert ® assays and HPV Genotypes 14 Real-TM Quant. Peripheral blood mononuclear cells were used for HTLV-1 DNA detection. Differences in frequency distributions of characteristics between WLHIV with and without HR-HPV and HTLV-1 co-infections were assessed using the Chi-square tests.ResultsA total of 647 WLHIV enrolled in this study with a mean age of 42.8 years (SD 8.7); 93% were on ART for &amp;gt;1 year and 8.8% were not virally suppressed (&amp;gt;1000 HIV RNA copies/mL). The HTLV-1 positivity rate among WLHIV was 3.1% overall and 7.6% among those with HR-HPV. WLHIV with HR-HPV 31 had the highest proportion of HR-HPV/HTLV-1 co-infection (31.6%). In contrast, WLHIV with HR-HPV 39 had the lowest proportion of co-infection (7.1%). Participants with HR-HPV/HTLV-1 co-infections were older compared to those without the co-infections (35.2% vs. 23.3%). A higher proportion of women with HR-HPV/HTLV-1 co-infections had their sex debut before the age of 18 years (p=0.012). Women co-infected with HR-HPV/HTLV-1 were diagnosed with HIV at ≥ 35 years compared to those without infection (70.6% vs. 41.9%, p= 0.019).ConclusionWe found that HTLV-1 infection was more common among WLHIV on ART who also had HR-HPV and that co-infections were associated with the age of sexual debut and the age of HIV diagnosis.

Analysis of Programmed Cell Death-1 (PD-1) Gene Variations (re11568821 and rs41386349) in HTLV-1 Infection Using One Primer Pair and Proviral Load.

About 90% of people infected with Human T lymphotropic virus type-1 (HTLV-1) virus are asymptomatic, so it can be said that the prevalence of this virus is not completely clear. During chronic infection, the expression of programmed cell death-1 (PD-1) protein increases and causes exhausted phenotype in T cells. Considering the role of host genetics and immune responses in HTLV-1 infection, in this case-control study, included 81 asymptomatic carriers (ACs) and 162 healthy controls (HCs), rs11568821 and rs41386349 polymorphisms of PD-1 gene were evaluated by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method which investigated by one primer pair for both polymorphisms also, proviral load (PVL) measured by quantitative real-time PCR (Q-RT-PCR). The results showed that the mutant allele of rs11568821 (A) and rs41386349 (T) polymorphisms is associated with an increase in HTLV-1 infection significantly (p = 0.019 and p = 0.000 respectively). But there was no significant relationship between PVL and polymorphisms.

Epidemiological Features and Outcomes of HTLV-1 Carriers Diagnosed With Cancer: A Retrospective Cohort Study in an Endemic Country.

Human T-lymphotropic virus type 1 (HTLV-1) is an endemic virus in Latin America that is directly linked to adult T-cell leukemia/lymphoma (ATL). Previous studies have suggested an oncogenic role of HTLV-1 in non-ATL neoplasms and have found higher mortality in HTLV-1 carriers without ATL. In this retrospective cohort study, HTLV-1 carriers were identified through screening at a tertiary cancer center between 2006 and 2019. We compared the overall survival (OS) outcomes of patients with ATL with those with other solid or hematologic malignancies by sex stratification. We identified 1,934 HTLV-1 carriers diagnosed with cancer. The median age at diagnosis was 62 (range 20-114) years, 76% were female, 60% had no or elementary school education, and 50% were born in the Andean highlands. The most common non-ATL neoplasm was cervical cancer (50%) among females and non-ATL non-Hodgkin lymphoma (26%) among males. With a median follow-up of 66 months, the 5-year OS of HTLV-1 carriers with non-ATL neoplasms (26%-47% for females and 22%-34% for males) was inferior to those reported in the general population. As expected, patients with ATL had a worse prognosis (5-year OS: 10% for females and 8% for males). HTLV-1 carriers with cancer were middle age and from underprivileged settings, suggesting an undetected transmission among vulnerable populations, especially females. Survival estimates of HTLV-1 carriers with non-ATL neoplasms were lower than the regional outcomes. Future research should ascertain how the biology of HTLV-1 and health care disparities affect the outcomes of HTLV-1 carriers, as well as determine the burden of HTLV-1 infection in the cancer population to recommend screening in the outpatient setting of endemic regions.

Inflammatory and anti-inflammatory responses in human T-lymphotropic virus Type 1 infection

Human T-lymphotropic virus Type 1 (HTLV-1) is a viral infectious agent that may cause chronic infection of T lymphocytes. HTLV-1 infection is related to multiple human diseases, including adult T-cell leukemia, which is a neoplastic growth of HTLV-1-infected T cells, and neoplastic inflammatory conditions such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), Sjögren’s syndrome, polymyositis uveitis, and bronchoalveolitis. T regulatory cells (Tregs), also known as regulatory T cells, and T helper 17 (Th17) cells, a distinct subset of cluster differentiation T cells with interleukin-17 as their major cytokine, orchestrate the pathogenesis of anti-inflammatory and inflammatory responses in HTLV-1-mediated diseases. In this review, we aim to evaluate the immune responses of Tregs as anti-inflammatory cells and Th17 cells as inflammatory cells in HTLV-1 infection.

Immigrating and vicinity are not risk factors in the prevalence and transmission rate of human T-lymphotropic virus type 1: A Survey in an endemic region of Iran and Afghan refugees.

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with two life-threatening diseases; HAM/TSP and ATLL. Due to the slow-growing HTLV-1 infection worldwide, WHO urged for elimination. A large border with Afghanistan, northeast Iran is an endemic region for HTLV-1 infection. Historically, Afghanistan has common sociocultural similarities to Persian peoples. This study was conducted to evaluate HTLV-1 prevalence in Afghan refugees. Also, the HTLV-1 transmission rate and understanding of whether or not the Silk Road has been the route of HTLV-1 infection to Iran were investigated. This case-control study was conducted in a rural area of Fariman city, with Afghan residents who migrated around 165 years ago, from 1857, the Treaty of Paris at the end of the Anglo-Persian war, and a refugee camp in Torbat-e-Jam city. These populations in HTLV-1 endemic area were compared to a segregated population of Afghan refugees in Semnan, the centre of Iran. Blood samples of 983 volunteers were assessed with the ELISA method for the presence of HTLV-1 antibodies and then confirmed by PCR technique. All samples from Afghan refugee camps, Semnan and Torbat-e-Jam, were negative for HTLV-1 infection. However, the prevalence of HTLV-1 infection in Fariman, a rural population of Afghan origin, was approximately 2.73%. The results showed that HTLV-1 is not endemic in Afghanistan, a war-stricken region with refugees distributed worldwide. The land Silk Road has not been the route of HTLV-1 transmission to Northeastern Iran. Importantly, HTLV-1 endemicity might occur during a long time of living in an endemic area.

Hematological changes in human lymphotropic-T virus type 1 carriers.

The human T-lymphotropic virus type 1 (HTLV-1), isolated in 1980, causes T-cell leukemia/lymphoma in adulthood, a type of lymphoproliferative disease, and chronic HTLV-1-associated myelopathy, a disease that causes paralysis of the lower limbs, which occur in about 5% of cases in this viral infection. This study aimed to establish the hematological profile of patients with HTLV-1 infection in Belém do Pará, describing the hematological parameters under study, estimating the frequency of lymphocytic atypical, and associating the hematological profile with diseases and symptoms. Hematologic data from 202 individuals were analyzed, including 87 HTLV-1 infected individuals and 115 non-HTLV-1 infected individuals as a control group, composed, at a great part, of relatives of the infected. The seroprevalence of HTLV-1 infection was observed in 71.3% of female individuals, with predominance in the group older than 50 years (44.8%). The analysis of hematological parameters showed a significant difference in the counts of the segmented cells (p = 0.0303) and eosinophils (p = 0.0092) in HTLV-1 carriers. Lymphocytic atypical was a finding present only in HTLV-1 carriers (p = 0.0001). There was no high frequency in the leukocyte counts of those infected by HTLV-1 not among them concerning a significant increase or decrease. It is concluded that HTLV-1 infection is prominent in women over 50 years old. The hematological profile of those infected shows a reduction of segmented cells, an increase of eosinophils, and the presence of atypical lymphocytes. The hematological profile of the HTLV-1 carrier should always be evaluated to identify early some diseases associated with the infection.

Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as an additional or alternative CSF biomarker to identify HAM/TSP patients with a worse prognosis.

Radiographic aspects in individuals infected by human T-lymphotropic virus type 1 (HTLV-1) with joint pain

BackgroundJoint pain in the absence or with little synovitis is observed in a large percentage of HTLV-1 infected subjects. As the virus infect CD4 + and CD8 + positive, macrophages and B cells an exaggerated production of pro-inflammatory cytokines is detected in these patients. However, the possible association of HTLV-1 infection with autoimmune diseases has not been documented definitively and the clinical characteristics of HTLV-1 associated arthropathy has not been defined. The objective this study is to describe clinic and radiographic features in HTLV-1-infected individuals with complaints of joint pain.MethodsCross-sectional study enrolling HTLV-1-infected individuals with chronic joint pain, aged up to 75 years, both genders and seronegative controls with osteoarthritis. All participants underwent conventional radiography of the hips, knees and ankles.ResultsEighty-one HTLV-1 infected patients and 30 subjects with osteoarthritis participated in the study. Polyarticular and symmetrical arthritis prevailed in the HTLV-1 positive group (54%), while oligoarticular and asymmetrical (44%) were more common in controls (p < 0.05). The frequency of enthesophytes (90%) in HTLV-1-infected patients was greater than in the control group (73%) (p < 0.05). Radiographic features were similar in HTLV-1 carriers and in patients with probable or definite HTLV-1 associated myelopathy. The presence of enthesophytes in the absence of joint space reduction or osteophytes was only observed in HTLV-1-infected individuals (p < 0.001). Magnetic resonance imaging of the ankles of five HTLV-1-infected patients and five controls demonstrated a higher frequency of enthesitis, bursitis and osteitis in the HTLV-1 infected group.ConclusionHTLV-1-associated arthropathy is clinically characterized by symmetrical polyarthralgia and the main radiological finding is the presence of enthesophytes in the absence of osteophytes and joint space narrowing.

Prevalence of Human T-Lymphotropic Virus Type 1 in Brain-Dead Organ Donors

Background: This study aimed to assess the prevalence of human T-lymphotropic virus type 1 (HTLV-1) among brain-dead organ donors at Masih Daneshvari Hospital in Tehran, Iran. Methods: By enzyme-linked immunosorbent assay (ELISA), 54 organ donors were screened for HTLV-1 virus in this descriptive cross-sectional study. Following that, Western blot confirmation was performed to confirm the HTLV-I infection. Results: Anti-HTLV-1 antibodies were detected in 2 (3.4%) cases out of 54 patients tested by ELISA. A western blot was performed in cases of positive results, but none of the subjects tested positive for HTLV-1 infection. Conclusions: The results of the present study indicated rare cases of HTLV-I infection in brain-dead organ donors. However, it is recommended that organ donors be investigated for the prevalence of this virus.

Th17 Cells and Tregs in HTLV-1 Infection

HTLV-1 (human T-lymphotropic virus type 1) causes chronic infection of human T lymphocytes. HTLV-1 infection is known to be related to multiple diseases, including neoplastic growth of HTLV-1-infected T cells (ATL) and neoplastic inflammatory conditions, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), Sjögren’s syndrome with arthritis, polymyositis uveitis, and bronchoalveolitis. Regulatory T cells (Tregs) regulate inflammatory cells, such as Th17 cells. The purpose of this study was to evaluate Tregs and Th17 cells, as well as the expression of related transcription factors (ROR-?t and FOXP3) and cytokines (IL-10, TGF-?, IL-6, and IL-17A) in HTLV-1 infection.

Evaluation of Strongyloides stercoralis infection in patients with HTLV-1.

Introduction: Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response.Objective: To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil.Materials and methods: We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot.Results: The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S. stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/ gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178). Conclusions: HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.

Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection.

Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.

HTLV-1 and Co-infections.

Human T lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes lifelong T-cell infection in humans, impacting the host immune response. This virus causes a range of clinical manifestations, from inflammatory conditions, including neuronal damage (HTLV-1 associated myelopathy, HAM) to life-threatening leukemia (adult T-cell leukemia, ATL). Human T lymphotropic virus type 1 is also associated with increased risk of all-cause mortality, but the mechanisms remain unclear. As a blood-borne and sexually transmitted infection (STI), HTLV-1 shares transmission routes to many other pathogens and although it has worldwide distribution, it affects mainly those in low- and middle-income tropical areas, where the prevalence of other infectious agents is high. These factors contribute to a high incidence of co-infections in people living with HTLV-1 (PLHTLV). This comprehensive review addresses the impact of HTLV-1 on several co-infections and vice-versa. There is evidence of higher rates of HTLV-1 infection in association with other blood borne (HCV, HBV) and sexually transmitted (Syphilis, Chlamydia, HPV, HSV) infections but whether this represents increased susceptibility or opportunity is unclear. Higher frequency of Mycobacterium tuberculosis (MTb) and Mycobacterium leprae (M. leprae) is observed in PLHTLV. Reports of opportunistic infections and high frequency of crusted scabies in patients with HTLV-1 points to immune impairment in those individuals. Human T lymphotropic virus type 1 may influence the persistence of pathogens, exemplified by the higher rates of Schistosoma mansoni and Strongyloides stercoralis (St. stercoralis) treatment failure observed in PLHTLV. This retrovirus is also associated with increased tuberculosis (TB) severity with some evidence pointing to a deleterious impact on leprosy outcome as well. These findings are supported by immune alterations observed in those co-infected individuals. Although the role of HTLV-1 in HCV outcome is debatable, most data indicate that HTLV may negatively impact the clinical course of hepatitis C. Co-infections may also influence the risk of developing HTLV-1 associated disease, but data are still limited. The impact of HTLV-1 on the response to more common infections, might contribute to the increased mortality rate of HTLV-1. Large scale prospective controlled studies on the prevalence and impact of HTLV-1 in co-infections and vice-versa are needed. Human T lymphotropic virus type 1 impact in public health is broad. Measures to increase awareness and to prevent new infections are needed.

Work ability and associated factors in people living with human T-cell leukemia virus type 1

ABSTRACTBackground: Infection with the human T-lymphotropic virus type 1 (HTLV-1) affects an estimated 10-15 million people worldwide. However, knowledge of the impact of HTLV-1 infection on work ability is lacking. This study aimed to measure the frequency and identify factors associated with poor work ability in patients living with HTLV-1. Methods: This cross-sectional study included 207 individuals infected with HTLV-1 who attended the University Hospital in Salvador, Bahia, Brazil. HTLV-1 antibodies were detected in the participants’ blood by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blotting. Participants answered a questionnaire on sociodemographic data, personal habits, clinical data, health-related quality of life, and work ability, evaluated using the work ability index questionnaire. A Poisson regression model with a robust variance estimate was used to identify the factors associated with the prevalence of poor work ability.Results: Patients mean age was 55.2, ranging from 19 to 84 years, 73.0% were females, 100% had monthly family income less than US$ 394, and 33.8% presented HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). No individual was classified as having excellent work ability. Poor work ability prevalence was strongly associated (prevalence ratio; 95% confidence interval [CI]) with sedentarism (1.30; 1.03-1.65), neurological symptoms (1.25; 1.02-1.52), and low physical (0.95; 0.94-0.96) and mental (0.98; 0.97-0.99) component summaries of health-related quality of life.Conclusions: Poor work ability among people living with HTLV-1 is associated with sedentarism, neurologic symptoms, and low health-related quality of life.

[Expression of integrins β1, α4 and cell adhesion molecule ICAM-1 in the presence of sodium deoxyribonucleate with ferrum complex (DNA-Na-Fe) by MT-4 cells transformed by human T-lymphotropic virus type 1 (Retroviridae: Orthoretrovirinae: Deltaretrovirus: Human T-lymphotropic virus type 1)].

The important role of integrins (IG) in the initiation and development of cancer processes makes these structures convenient targets for the development of immunomodulatory therapeutic drugs that have an effect directly on these molecules. Among the latter, IG β1, α4 and cell adhesion receptor ICAM-1 (intercellular adhesion molecule 1) are of particular interest. Immunomodulators are capable of changing the IG activity through non-specific mechanisms, which, however, in some cases can cause a decrease in the protective functions of the immune system and health deterioration.The aim of the study was to determine the effect on the levels of cellular expression and the nature of IG metabolism of the drug sodium deoxyribonucleate with ferrum complex, DNA-Na-Fe, which is having been used in the Russian Federation as an immunomodulatory agent, but whose action has not been studied in details so far. We used 2 variants of the neoplastic CD4+ T-lymphocyte cell line transformed with human T-lymphotropic virus type 1 (HTLV-1) of the Retroviridae family, MT-4 (MT-4/1 and MT-4/2). The indicated variants were characterized by different levels of expression of the protein activation markers CD28 and CD38. After cell culture in the presence of 500 μg/ml DNA-Na-Fe, the expression levels of IG β1 (CD29), α4 (CD49d), and ICAM-1 (CD54) were studied by flow cytometry. The cells of the both lines contained many membrane proteins CD29+ (90.4% ± 4.5) and CD54+ (97.9% ± 1.4), while small percentage of cells contained protein CD49d+ (1.9% ± 1.0). No changes in the expression of the studied proteins were observed in the presence of the drug. The levels of IG β1, α4 and ICAM-1 expression may serve as one of the phenotypic characteristics of MT-4 cells. The obtained data are of great importance because the peculiarities of CD4+ T-lymphocytes transformation and their metabolism during HTLV-1 infection have not been sufficiently studied so far. The results of this work may be helpful in determining the pathogenesis of HTLV-1-induced diseases, some types of malignancies, and in searching for new specific pharmacological agents, including molecularly targeted ones. The results of the study will help to expand the existing knowledge on the markers of MT-4 cell line.

The novel roles of virus infection-associated gene CDKN1A in chemoresistance and immune infiltration of glioblastoma.

Chemoresistance is a common limitation for successful treatment of glioblastoma multiforme (GBM). Recently, virus infections have been demonstrated to be associated with tumorigenesis and chemoresistance in tumors. However, the role of infection-related genes in GBM haven’t been clearly demonstrated. Here, we explored the roles and mechanisms of human T-lymphotropic virus type-1 (HTLV-1) infections in tumorigenesis and chemoresistance in GBM. Four candidate genes, CDKN1A, MSX1, MYC and CHEK2, were identified to be the codifferentially expressed genes between three temozolomide (TMZ) chemotherapy datasets and one HTLV-1 infection gene set. Next, comprehensive bioinformatics data from several databases indicated that only CDKN1A was significantly upregulated in both GBM tissues and cells and showed the greatest prognostic value in GBM patients. Clinical data identified the correlations between CDKN1A expression and clinicopathological parameters of GBM patients. Moreover, CDKN1A was found to be involved in AKT-mediated TMZ resistance of glioma cells. In addition, KEGG analysis of CDKN1A-associated coexpression genes showed that CDKN1A was potentially involved in complement and coagulation cascades pathways in GBM. Finally, TISIDB database was used to investigate the role of CDKN1A in tumor-immune system interactions in GBM. These findings enhanced our understanding of the roles of CDKN1A in tumorigenesis and therapy response in GBM.