Результаты поиска

Absence of consistent association between human leukocyte antigen-I and -II alleles and human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis risk in an HTLV-1 French Afro-Caribbean population.

OBJECTIVES: Human T-cell lymphotropic virus type 1 (HTLV-1) infection leads to the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in less than 5% of cases. The mechanism of disease progression in HAM/TSP remains unknown. A significant role of certain human leukocyte antigen (HLA) genotypes in determining the risk of HAM/TSP has been reported in Japan, where the HLA-A*02 gene has been found to be associated with a lower HTLV-1 provirus load and with protection from HAM/TSP, whereas HLA-DRB1*0101 has been found to be associated with an increased susceptibi

[HTLV-1 and HTLV-2 proviral load: a simple method using quantitative real-time PCR].

When the human T cell lymphotropic virus (HTLV) is integrated with the host cell genome (provirus), its proviral DNA is a replication marker. Proviral load appears to be an important factor in the development of diseases related to these retroviruses. In this study, a methodology for absolute quantification of the HTLV-1 and HTLV-2 proviral load using real-time PCR was developed. Fifty-three blood donor samples with positive ELISA test result were subjected to this methodology, which utilized the TaqMan system for three target sequences: HTLV-1, HTLV-2 and albumin. The absolute proviral load w

In vivo fluctuation of HTLV-I and HTLV-II proviral load in patients receiving antiretroviral drugs.

HTLV-I and HTLV-II infect T lymphocytes. A high HTLV-I proviral load in peripheral blood mononuclear cells (PBMCs) has been associated with a higher risk of neurologic disease. For HTLV-II, large numbers of infected lymphocytes might contribute to accelerate the immunodeficiency and increase the risk of neuropathy in HTLV-II/HIV-1 coinfected people. We have examined the impact of antiretroviral drugs on HTLV proviral load, testing longitudinal samples collected from 1 HTLV-I infected patient suffering HTLV-I-associated myelopathy (HAM), and two HTLV-II/ HIV-1 coinfected subjects. The HAM patie

Inhibition of murine AIDS by combination of AZT and dideoxycytidine 5'-triphosphate.

A combination of antiretroviral drugs acting on different cell types (lymphocytes and macrophages) was evaluated in a murine retrovirus-induced immunodeficiency model of AIDS (MAIDS). In a first experiment, C57BL/6 mice were infected with a single i.p. administration of LP-BM5 and treated with 0.125 or 0.25 mg/ml AZT in drinking water for 3 months. AZT treatment was found to reduce lymphadenopathy (60 and 65 percent, respectively), splenomegaly (37 and 50 percent, respectively), and hypergammaglobulinemia (6 and 50 percent, respectively). Furthermore, at the highest AZT concentration, BM5d pro

Detection of the products of polymerase chain reaction by an ELISA system based on an ion sensitive field effect transistor.

An ELISA system was developed using a pH sensitive ISFET (pH-FET) as a detector, a pipette tip as a solid phase, and urease as a detecting enzyme. Double stranded PCR products with digoxigenin and biotin at both terminals were obtained by using digoxigenin- and biotin-labeled primers. 1 microliters of the PCR solution was directly introduced into the end part of a pipette tip coated with anti-digoxigenin antibody. Biotin-labeled PCR products captured at the solid phase were detected with avidin-urease, of which the activity was measured by a pH-FET in a pH-measuring cell containing urea soluti

Virtual Screening of FDA-Approved Compounds: Exploring New Alternatives for HIV Treatment.

Human immunodeficiency virus (HIV) infection remains a significant public health challenge, particularly because of the emergence of drug-resistant strains against the drugs currently used in highly active antiretroviral therapy (HAART). The ongoing search for new molecules with therapeutic potential remains crucial. In this study, a virtual screening approach was employed to identify novel candidates with therapeutic potential for HIV. High-throughput screening (HTS) data were used to train and validate quantitative structure-activity relationship (QSAR) models, which were subsequently applie

Совпадение в полном тексте источника
… Armani-Tourret and colleagues demonstrated that the combined administration of panobinostat and interferon resulted in a decrease in nonclonal intact proviruses, a reduction in the structural and phylogenetic complexity of intact proviruses, and an increase in the number of proviruses with 5-LTR deletions … While such effects may occur naturally during long-term HAART, they appear to be accelerated by the described protocol, indicating that HIV-1 proviruses may be rendered and sensitized for immunological clearance. …

CRISPR-mediated excision of HTLV-1 reduces proviral loads in PBMCs from HAM/TSP patients.

CRISPR technology is emerging as a promising therapeutic approach for eliminating chronic viral infections, such as herpesviruses and HIV. Here, for the first time, we demonstrate in vitro that CRISPR can be used to excise the HTLV-1 genome and reduce proviral loads in PBMCs from HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) patients. Single treatment with CRISPR-RNP (ribonucleoprotein) complexes composed of two gRNAs targeting the HTLV-1 env gene and 3'LTR sequences resulted in excision of a 2613 bp segment of the proviral genome, spanning tax and HBZ genes, without dete

Mannose receptor may be involved in small ruminant lentivirus pathogenesis.

Thirty-one sheep naturally infected with small ruminant lentiviruses (SRLV) of known genotype (A or B), and clinically affected with neurological disease, pneumonia or arthritis were used to analyse mannose receptor (MR) expression (transcript levels) and proviral load in virus target tissues (lung, mammary gland, CNS and carpal joints). Control sheep were SRLV-seropositive asymptomatic (n = 3), seronegative (n = 3) or with chronic listeriosis, pseudotuberculosis or parasitic cysts (n = 1 in each case). MR expression and proviral load increased with the severity of lesions in most analyzed org

Bryostatin-1 synergizes with histone deacetylase inhibitors to reactivate HIV-1 from latency.

The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication on patients treated with HAART. It has been suggested that successful depletion of such latent reservoirs will require a combination of therapeutic agents that can specifically and efficiently act on cells harboring latent HIV-1 provirus. Using Jurkat-LAT-GFP cells, a tractable model of HIV-1 latency, we have found that bryostatin -1 reactivates HIV-1 through a classical PKC-dependent pathway. Bryostatin-1 also activates MAPKs and NF-κB pathways and synergizes with HDAC inhibitors to rea

Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report.

BACKGROUND: Although drug resistance is a major challenge in HIV therapy, the effect of drug resistance mutations on HIV evolution in vivo is not well understood. We have now investigated genetic heterogeneity in HIV-1 by performing drug resistance genotyping of the PR-RT regions of viruses derived from plasma and peripheral blood mononuclear cells (PBMCs) of a single patient who had failed multiple regimens of anti-retroviral therapy. RESULTS: Patterns of drug resistance mutations showed that the viral populations in PBMCs were more heterogeneous than in plasma. Extensive analysis of HIV fro

Detection of HTLV-1 by polymerase chain reaction in situ hybridization in adult T-cell leukemia/lymphoma.

A method for nonradioactive polymerase chain reaction in situ hybridization was developed and used to determine the distribution of human T-lymphotropic virus type I (HTLV-I) proviral DNA in paraffin-embedded surgical specimens of adult T-cell leukemia/lymphoma (ATLL). As controls, we used biopsy samples of five cases of mycosis fungoides, cells of an HTLV-I-infected cell line (MT2), as well as HTLV-1-negative cells (YAS). We successfully detected the amplicon of the HTLV-1 tax sequence in the nuclei of the cutaneous infiltrating lymphoid cells in 90% (9/10) of ATLL cases. Studies also reveale

Relationship between anti-Tax antibody responses and cocultivatable virus in HTLV-I-infected rabbits.

The presence of anti-Tax antibody responses in human T cell leukemia virus type I (HTLV-I)-infected individuals has been correlated with increased proviral load, increased risk of transmitting infection, and increased risk of developing tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In this study, a rabbit model of HTLV-I infection was used to determine whether anti-Tax antibody responses could predict the presence of virus with the potential to replicate. Seven of 14 HTLV-I-infected rabbits developed anti-Tax antibody responses. The onset of Tax reactivity was variable,

Impact of Proviral-DNA M184V/I on 96-Week Outcomes of DTG/3TC Maintenance Therapy: Results From the VOLVER Clinical Trial.

BACKGROUND: The effect of archived lamivudine resistance mutations in the efficacy of dolutegravir plus lamivudine (DTG/3TC) remains unclear. We evaluated whether proviral-DNA M184V/I detection is associated with virological outcomes in the VOLVER-GESIDA 11820 study. METHODS: This open-label, single-arm, multicenter phase IIa trial (NCT04880785) enrolled virologically suppressed adults with documented or suspected historical lamivudine resistance if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Participants switched to DTG/3TC and were followed through

Latent reservoirs in memory T cell subsets are linked to poor immune recovery in people living with HIV.

Highly active antiretroviral therapy (HAART) suppresses viral loads in 71% of people living with HIV globally, while failing to bring adequate immune reconstitution in nearly one-third of them. We hypothesize that the persistence of latent HIV reservoirs in specific memory T cell subsets contributes to impaired immune recovery. We conducted a case-control study to estimate differences in the HIV-1 proviral DNA across memory CD4-positive T cell subsets between participants with CD4 counts of over 500 cells/µL (immune responders or IRs) and those with counts of less than 350 cells/µL (immune non

The dual-target approach in viral HIV-1 viremia testing: An added value to virological monitoring?

New methods of HIV-1 RNA quantification based on dual-target detection are increasingly used in HIV viral load monitoring, but clinical implications and impact of dual-target detection on HIV-1 infection management are not established. Aptima HIV-1 Quant Dx assay is a last generation HIV viral load method, that uses pol and LTR as simultaneous target, providing quantitative results based mainly on pol target, while LTR target is used to report the results when pol signal is absent. In our laboratory, about 6% of results of all HIV-1 viral load tests performed with this platform in one year per

Neurologic, clinical, and immunologic features in a cohort of HTLV-1 carriers with high proviral loads.

A high proviral load (PVL) is recognized as a risk factor for human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but there is a lack of prospective studies evaluating whether or not HTLV-1 carriers with high PVL are at risk of developing HAM/TSP or other HTLV-1-related diseases. Here, we compare the incidence of clinical manifestations and the cytokine levels in 30 HTLV-1 carriers with high (> 50,000 copies/106 PBMC) and an equal number of subjects with low proviral load. Participants were followed for 3 to 16 years (median of 11 years). The PVL, IFN-γ,

Routine drug resistance testing in HIV-1 proviral DNA, using an automated next- generation sequencing assay.

BACKGROUND: HIV-1 DNA genotypic drug resistance testing is increasingly performed to guide treatment switching or simplification in controlled patients. The Sentosa NGS platform is a fully automated system marketed for drug resistance testing on HIV-1 RNA samples. OBJECTIVES: The aim of this study was to evaluate this automated NGS solution for routine resistance genotypic resistance testing in proviral HIV-1 DNA. STUDY DESIGN: Sanger sequencing (SS) of the reverse transcriptase (RT), protease (PR) and integrase (IN) genes was performed using the French ANRS protocol. NGS was performed retro

HEXIM1-Tat chimera inhibits HIV-1 replication.

Transcription of HIV provirus is a key step of the viral cycle, and depends on the recruitment of the cellular positive transcription elongation factor b (P-TEFb) to the HIV promoter. The viral transactivator Tat can displace P-TEFb from the 7SK small nuclear ribonucleoprotein, where it is bound and inactivated by HEXIM1, and bring it to TAR, which allows the stalled RNA polymerase II to transition to successful transcription elongation. In this study, we designed a chimeric inhibitor of HIV transcription by combining functional domains from HEXIM1 and Tat. The chimera (HT1) potently inhibited

Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians.

BACKGROUND: The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). METHODOLOGY/PRINCIPAL FINDINGS: 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of ches

Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by targeting and eliminating infected CCR4-expressing cells in vitro and in vivo.

BACKGROUND: Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) infection. However, there are no therapies to prevent ATL development in high-risk asymptomatic carriers. To develop a therapy targeting HTLV-1-infected cells that are known to express CCR4 frequently, we tested whether truncated Pseudomonas exotoxin (PE38) fused to a CCR4 ligand, CCL17/thymus and activation-regulated chemokine (TARC), selectively eliminates such cells. RESULTS: Our data show that TARC-PE38 efficiently killed HTLV-1-infected cell lines. It also shrank HTLV-1-associated solid tumor