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Viruses Sep 2023The main mode of mother-to-child transmission of the human T-cell leukemia virus (HTLV)-1 is through breastfeeding. Although the most reliable nutritional regimen to... (Review)
Review
The main mode of mother-to-child transmission of the human T-cell leukemia virus (HTLV)-1 is through breastfeeding. Although the most reliable nutritional regimen to prevent HTLV-1 transmission is exclusive formula feeding, a recent meta-analysis revealed that short-term breastfeeding within 90 days does not increase the risk of infection. The protocol of the Japanese Health, Labor, and Welfare Science Research Group primarily recommended exclusive formula feeding for mothers who are positive for HTLV-1. However, there has been no quantitative research on the difficulties experienced by HTLV-1-positive mothers in carrying out these nutritional regimens, including the psychological burden. Therefore, this review was performed to clarify the burdens and difficulties encountered by mothers who are positive for HTLV-1; to this end, we analyzed the data registrants on the HTLV-1 career registration website "Carri-net" website. The data strongly suggest that it is not sufficient to simply recommend exclusive formula feeding or short-term breastfeeding as a means of preventing mother-to-child transmission; it is important for health care providers to understand that these nutritional regimens represent a major burden for pregnant women who are positive for HTLV-1 and to provide close support to ensure these women's health.
Topics: Humans; Female; Pregnancy; Infant; Human T-lymphotropic virus 1; Mothers; Infectious Disease Transmission, Vertical; Japan; Leukemia, T-Cell
PubMed: 37896779
DOI: 10.3390/v15102002 -
Frontiers in Public Health 2023Migratory flows play a significant role in the spread of human T-lymphotropic virus 1/2 (HTLV-1/2). In the last decade, a substantial migration of individuals occurred...
INTRODUCTION
Migratory flows play a significant role in the spread of human T-lymphotropic virus 1/2 (HTLV-1/2). In the last decade, a substantial migration of individuals occurred from Haiti and Venezuela to Brazil. However, data on the prevalence of HTLV-1/2 infection among these international migrants in Brazil are scarce. This study describes the prevalence of this infection among immigrants and refugees in Central Brazil.
METHODS
A cross-sectional study was conducted with 537 international migrants in the State of Goiás, Central Brazil. Participants were interviewed, and blood samples were collected. Serological screening for anti-HTLV-1/2 was performed using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I + II, DiaSorin, Dartford, UK), and seropositive samples were submitted for confirmation by a line immunoassay (INNO-LIA HTLV I/II, Fujirebio, Europe N.V., Belgium).
RESULTS
The majority of participants were males (54.4%), between 18 and 50 years old (78%; mean age: 29.1 years), self-declared black (55.1%), reported 1 to 12 years of formal education (70.9%), and were either Venezuelans (47.9%) or Haitians (39.7%). Additionally, 50.1% were immigrants, 49% were refugees, and five were Brazilian children (0.9%) born to Haitian immigrant parents. The overall prevalence of anti-HTLV-1/2 was 0.95% (95% CI: 0.31-2.28), with HTLV-1 at 0.19% and HTLV-2 at 0.76%. All seropositive individuals ( = 5) were refugees from Venezuela, resulting in a rate of 2.26% for anti-HTLV-1/2, HTLV-1 (0.45%) and HTLV-2 (1.81%) among Venezuelan refugees. Of the demographic and behavioral characteristics evaluated, unprotected sexual intercourse and having more than one sexual partner (≥2) in the previous 12 months were associated with HTLV-1/2 seropositivity among Venezuelans.
CONCLUSION
This study revealed, despite the low seroprevalence of HTLV-1/2 among international migrants in Central Brazil, evidence of HTLV-1 and HTLV-2 infections in Venezuelan refugees. In addition, their characteristics highlight that specific social and health programs should be implemented for these emergent and socially vulnerable migrant groups.
Topics: Male; Child; Humans; Adult; Adolescent; Young Adult; Middle Aged; Female; Human T-lymphotropic virus 1; Brazil; Cross-Sectional Studies; Seroepidemiologic Studies; Haiti; Refugees; Vulnerable Populations; HTLV-I Infections; Human T-lymphotropic virus 2; Emigrants and Immigrants
PubMed: 37869208
DOI: 10.3389/fpubh.2023.1265100 -
Journal of Virology Feb 2024The primary mode of infection by human T-cell leukemia virus type 1 (HTLV-1) is cell-to-cell transmission during contact between infected cells and target cells....
The primary mode of infection by human T-cell leukemia virus type 1 (HTLV-1) is cell-to-cell transmission during contact between infected cells and target cells. Cell-free HTLV-1 infections are known to be less efficient than infections with other retroviruses, and transmission of free HTLV-1 is considered not to occur . However, it has been demonstrated that cell-free HTLV-1 virions can infect primary lymphocytes and dendritic cells , and that virions embedded in biofilms on cell membranes can contribute to transmission. The establishment of an efficient cell-free HTLV-1 infection model would be a useful tool for analyzing the replication process of HTLV-1 and the clonal expansion of infected cells. We first succeeded in obtaining supernatants with high-titer cell-free HTLV-1 using a highly efficient virus-producing cell line. The HTLV-1 virions retained the structural characteristics of retroviruses. Using this cell-free infection model, we confirmed that a variety of cell lines and primary cultured cells can be infected with HTLV-1 and demonstrated that the provirus was randomly integrated into all chromosomes in the target cells. The provirus-integrated cell lines were HTLV-1-productive. Furthermore, we demonstrated for the first time that cell-free HTLV-1 is infectious using a humanized mouse model. These results indicate that this cell-free infection model recapitulates the HTLV-1 life cycle, including entry, reverse transcription, integration into the host genome, viral replication, and secondary infection. The new cell-free HTLV-1 infection model is promising as a practical resource for studying HTLV-1 infection.IMPORTANCECo-culture of infected and target cells is frequently used for studying HTLV-1 infection. Although this method efficiently infects HTLV-1, the cell mixture is complex, and it is extremely difficult to distinguish donor infected cells from target cells. In contrast, cell-free HTLV-1 infection models allow for more strict experimental conditions. In this study, we established a novel and efficient cell-free HTLV-1 infection model. Using this model, we successfully evaluated the infectivity titers of cell-free HTLV-1 as proviral loads (copies per 100 cells) in various cell lines, primary cultured cells, and a humanized mouse model. Interestingly, the HTLV-1-associated viral biofilms played an important role in enhancing the infectivity of the cell-free infection model. This cell-free HTLV-1 infection model reproduces the replication cycle of HTLV-1 and provides a simple, powerful, and alternative tool for researching HTLV-1 infection.
Topics: Animals; Humans; Mice; HTLV-I Infections; Human T-lymphotropic virus 1; Lymphocytes; Proviruses; Virus Replication; Cell-Free System; Cell Line; Cells, Cultured; Virus Internalization; Reverse Transcription; Biofilms; Virus Integration
PubMed: 38294250
DOI: 10.1128/jvi.01862-23 -
Journal of Neurology Jun 2024Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter,... (Randomized Controlled Trial)
Randomized Controlled Trial
Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy.
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (- 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60-80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
Topics: Humans; Double-Blind Method; Antibodies, Monoclonal, Humanized; Male; Middle Aged; Female; Paraparesis, Tropical Spastic; Adult; Aged; Neopterin; Human T-lymphotropic virus 1; Chemokine CXCL10; Viral Load; Treatment Outcome
PubMed: 38430272
DOI: 10.1007/s00415-024-12239-x -
One Health (Amsterdam, Netherlands) Jun 2024Peru was one of the most affected countries during the COVID-19 pandemic. Moreover, multiple other viral diseases (enteric, respiratory, bloodborne, and vector-borne)...
Peru was one of the most affected countries during the COVID-19 pandemic. Moreover, multiple other viral diseases (enteric, respiratory, bloodborne, and vector-borne) are endemic and rising. According to Peru's Ministry of Health, various health facilities in the country were reallocated for the COVID-19 pandemic, thereby leading to reduced action to curb other diseases. Many viral diseases in the area are under-reported and not recognized. The One Health approach, in addition to clinical testing, incorporates environmental surveillance for detection of infectious disease outbreaks. The purpose of this work is to use a screening tool that is based on molecular methods, high throughput sequencing and bioinformatics analysis of wastewater samples to identify virus-related diseases circulating in Trujillo-Peru. To demonstrate the effectiveness of the tool, we collected nine untreated wastewater samples from the Covicorti wastewater utility in Trujillo-Peru on October 22, 2022. High throughput metagenomic sequencing followed by bioinformatic analysis was used to assess the viral diversity of the samples. Our results revealed the presence of sequences associated with multiple human and zoonotic viruses including Orthopoxvirus, Hepatovirus, Rhadinovirus, Parechovirus, Mamastrovirus, Enterovirus, Varicellovirus, Norovirus, Kobuvirus, Bocaparvovirus, Simplexvirus, Spumavirus, Orthohepevirus, Cardiovirus, Molliscipoxvirus, Salivirus, Parapoxvirus, Gammaretrovirus, Alphavirus, Lymphocryptovirus, Erythroparvovirus, Sapovirus, Cosavirus, Deltaretrovirus, Roseolovirus, Flavivirus, Betacoronavirus, Rubivirus, Lentivirus, Betapolyomavirus, Rotavirus, Hepacivirus, Alphacoronavirus, Mastadenovirus, Cytomegalovirus and Alphapapillomavirus. For confirmation purposes, we tested the samples for the presence of selective viruses belonging to the genera detected above. PCR based molecular methods confirmed the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), monkeypox virus (MPXV), noroviruses GI and GII (NoVGI and NoVGII), and rotavirus A (RoA) in our samples. Furthermore, publicly available clinical data for selected viruses confirm our findings. Wastewater or other environmental media surveillance, combined with bioinformatics methods, has the potential to serve as a systematic screening tool for the identification of human or zoonotic viruses that may cause disease. The results of this method can guide further clinical surveillance efforts and allocation of resources. Incorporation of this bioinformatic-based screening tool by public health officials in Peru and other Latin American countries will help manage endemic and emerging diseases that could save human lives and resources.
PubMed: 38798735
DOI: 10.1016/j.onehlt.2024.100756 -
Tropical Animal Health and Production Sep 2023Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a persistent infection and the most important neoplastic disease in cattle. It is spread primarily by...
Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a persistent infection and the most important neoplastic disease in cattle. It is spread primarily by transferring infected lymphocytes through blood from carriers to healthy animals. The present study is aimed at determining the seropositivity of BLV in breeding bulls from Costa Rica and at detecting for the first time in the country BLV DNA in bull semen. Between May 2011 and August 2018, 379 blood and 133 semen samples were collected from bulls distributed in 118 farms. The serum was analyzed by an enzymatic immunoassay and the semen by polymerase chain reaction and sequencing. BLV seropositivity was 43.5% (165/379), while 64.4% (76/118) of the farms had positive reactors. Holstein (75.7%) and Jersey (73.0%) breeds showed the highest seropositivity. In addition, Bos taurus bulls (68.1%), older than seven years (50.0%), and those belonging to dairy farms (75.5%) had higher seropositivity compared to Bos indicus (17.7%), younger than seven years (42.2%), and those from beef farms (15.5%), respectively. Moreover, Bos taurus bulls had a higher risk of being seropositive than Bos indicus (OR = 3.4; 95% CI: 1.7-6.8). BLV DNA was found in one semen sample (2.5%; 1/40) from a seropositive bull. The importance of serum and molecular BLV screening in semen samples and the potential role of some risk factors associated with the disease, such as the bull's age, genotype, and type of livestock productive system, is argued in the present report.
Topics: Cattle; Animals; Male; Semen; Enzootic Bovine Leukosis; Leukemia Virus, Bovine; Costa Rica; Seroepidemiologic Studies; Cattle Diseases
PubMed: 37777681
DOI: 10.1007/s11250-023-03763-5 -
Blood Advances Mar 2024Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine...
Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine biosynthesis in both normal T cells and ATL cells through regulation of uridine-cytidine kinase 2 (UCK2), which supports vigorous proliferation. UCK2 catalyzes the monophosphorylation of cytidine/uridine and their analogues during pyrimidine biosynthesis and drug metabolism. We found that UCK2 was overexpressed aberrantly in HTLV-1-infected T cells but not in normal T cells. T-cell activation via T-cell receptor (TCR) signaling induced expression of UCK2 in normal T cells. Somatic alterations and epigenetic modifications in ATL cells activate TCR signaling. Therefore, we believe that expression of UCK2 in HTLV-1-infected cells is induced by dysregulated TCR signaling. Recently, we established azacitidine-resistant (AZA-R) cells showing absent expression of UCK2. AZA-R cells proliferated normally in vitro, whereas UCK2 knockdown inhibited ATL cell growth. Although uridine and cytidine accumulated in AZA-R cells, possibly because of dysfunction of pyrimidine salvage biosynthesis induced by loss of UCK2 expression, the amount of UTP and CTP was almost the same as in parental cells. Furthermore, AZA-R cells were more susceptible to an inhibitor of dihydroorotic acid dehydrogenase, which performs the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, and more resistant to dipyridamole, an inhibitor of pyrimidine salvage biosynthesis, suggesting that AZA-R cells adapt to UCK2 loss by increasing de novo pyrimidine nucleotide biosynthesis. Taken together, the data suggest that fine-tuning pyrimidine biosynthesis supports vigorous cell proliferation of both normal T cells and ATL cells.
Topics: Adult; Humans; Pyrimidines; Uridine; Cell Proliferation; Cytidine; Human T-lymphotropic virus 1; Pyrimidine Nucleotides; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 38190613
DOI: 10.1182/bloodadvances.2023011131 -
Journal of Global Health Nov 2023
Topics: Humans; Human T-lymphotropic virus 1; Scabies
PubMed: 37921043
DOI: 10.7189/jogh.13.03057 -
PLoS Neglected Tropical Diseases Sep 2023Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been...
Epidemiological and molecular evidence of intrafamilial transmission through sexual and vertical routes in Bahia, the state with the highest prevalence of HTLV-1 in Brazil.
INTRODUCTION
Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been studied only in a few communities of Japanese immigrants and African-Brazilians.
OBJECTIVE
To investigate the familial clustering of HTLV-1 infection and to determine the likely routes of transmission through epidemiological and genetic analyzes.
METHODS
Medical records of 1,759 HTLV-1+ patients from de the Center for HTLV in Salvador, Brazil, were evaluated to identify first-degree relatives previously tested for HTLV-1. Familial clustering was assumed if more than one member of the same family was HTLV-1+. LTR regions of HTLV-1 sequences were analyzed for the presence of intrafamilial polymorphisms. Family pedigrees were constructed and analyzed to infer the likely transmission routes of HTLV-1.
RESULTS
In 154 patients at least one other family member had tested positive for HTLV-1 (a total of 182 first-degree relatives). Of the 91 couples (182 individuals), 51.6% were breastfed, and 67.4% reported never using a condom. Of the 42 mother-child pairs, 23.8% had a child aged 13 years or younger; all mothers reported breastfeeding their babies. Pedigrees of families with 4 or more members suggests that vertical transmission is a likely mode of transmission in three families. Three families may have had both vertical and sexual transmission routes for HTLV-1. The genetic signatures of the LTR region of 8 families revealed 3 families with evidence of vertical transmission, another 3 families (spouses) with sexual transmission, and one family with both transmission routes. HTLV-1 sequences belonged to Cosmopolitan subtype HTLV-1a Transcontinental subgroup A.
CONCLUSION
Sexual and vertical transmission routes contribute to the intrafamilial spread of HTLV-1 in the state of Bahia.
Topics: Infant; Female; Humans; Human T-lymphotropic virus 1; Brazil; Prevalence; HTLV-I Infections; Infectious Disease Transmission, Vertical; Mothers
PubMed: 37769013
DOI: 10.1371/journal.pntd.0011005 -
Virology Journal Aug 2023HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence...
BACKGROUND
HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely.
OBJECTIVE
To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms.
METHODS
Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated.
RESULTS
A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1 and HTLV-1 patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79-34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group.
CONCLUSION
The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.
Topics: Female; Humans; Middle Aged; Brazil; Cross-Sectional Studies; Human T-lymphotropic virus 1; Prevalence; Uveitis; Male
PubMed: 37605273
DOI: 10.1186/s12985-023-02135-7