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Defective human T-lymphotropic virus type 1 provirus in asymptomatic carriers.

Few studies have specifically examined defective provirus in asymptomatic human T-lymphotropic virus Type 1 (HTLV-1) carriers and its relation to proviral DNA loads (PVLs). To assess the significance of defective provirus in asymptomatic carriers, we examined PVLs in peripheral blood mononuclear cells of 208 asymptomatic HTLV-1 carriers. The mean PVLs determined using primers for the pol region were less than that for the pX region in these carriers. Analysis of seven carriers with high PVLs for the pX region but lower PVLs for the pol region showed that four had single nucleotide polymorphism

Granuloma annulare-like skin lesions as an initial manifestation in a Japanese patient with adult T-cell leukemia/lymphoma.

Granuloma annulare is characterized by noncaseating dermal granulomas with connective tissue changes. A relationship with hematologic and solid malignancies has been suggested in some cases. We describe a 70-year-old man who had erythematous annular plaques on his elbows, upper extremities, and wrists for a period of 3 months. Histologic examination revealed epithelioid cell granulomas associated with dense atypical lymphocytes in the dermis. Immunohistochemical staining of skin specimens showed a prominent infiltration of CD3+, CD4+, CD5+, and CD25+ cells. Human T-cell leukemia virus type I p

Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells.

To clarify the status of tax gene, we analyzed human T-cell leukemia virus type-I (HTLV-I) associated cell lines and fresh adult T-cell leukemia (ATL) cells. We compared 2 types of HTLV-I associated cell lines: one was derived from leukemic cells (leukemic cell line) and the other from nonleukemic cells (nonleukemic cell line). Although all nonleukemic cell lines expressed Tax, it could not be detected in 3 of 5 leukemic cell lines, in which nonsense mutation or deletion (60 bp) of tax genes, and DNA methylation in 5'-LTR were identified as the responsible changes. We found such genetic change

High circulating frequencies of tumor necrosis factor alpha- and interleukin-2-secreting human T-lymphotropic virus type 1 (HTLV-1)-specific CD4+ T cells in patients with HTLV-1-associated neurological disease.

Significantly higher frequencies of tumor necrosis factor alpha- and interleukin-2-secreting human T-lymphotropic virus type 1 (HTLV-1)-specific CD4(+) T cells were present in the peripheral blood mononuclear cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients than in those of asymptomatic carriers with similar provirus loads. The data suggest that HTLV-1-specific CD4(+) T cells play a role in the pathogenesis of HAM/TSP.

Unique morphological alterations of the HTLV-I transformed C8166 cells by infection with HIV-1.

C8166 cells express T lymphocyte markers, a monocyte-specific esterase, taxpolypeptide of HTLV-I. In spite of this transactivator, their HIV-1 yield is low. Their culture conditions were modified, and infected cells were immobilized on a poly-L-lysine sheet under semisolid overlays to study their phenotypic alterations and HIV-1 production by microscopy and electron microscopy. Another lymphoid cultures (MT-4, CEM, CEM-ss, AdCEM) similarly treated were infected with either HIV-1/RF or IIIB. Specificity of HIV-1 was compared to the effects of vesicular stomatitis virus (VSV). Unlike other cultu

Human T cell leukemia virus type I expression in salivary glands of infected patients.

Human T cell leukemia virus type I (HTLV-I) sequences were sought in labial salivary glands of patients with HTLV-I-associated myelopathy or tropical spastic paraparesis and of seropositive neurologically healthy carriers. HTLV-I proviral DNA was found by polymerase chain reaction amplification in DNA extracted from lip biopsies of every patient. Viral RNA was found by in situ hybridization in the acini epithelium, as well as in lymphocytic infiltrates. This observation suggests that HTLV-I expression in labial salivary glands could participate in the inflammatory lesions observed in these pat

Human immunodeficiency virus type 1 infection of mature CD3hiCD8+ thymocytes.

Although CD4+ cells are the primary targets of human immunodeficiency virus type 1 (HIV-1) infection, earlier reports have suggested that intrathymic infection of CD8+ cells may occur. However, it was unclear whether HIV-1-infected CD8+ thymocytes were truly mature single-positive (SP) cells. In the present study, SCID mice implanted with human fetal thymus and liver tissues (SCID-hu mice) were infected with three primary isolates of HIV-1 and infected thymocytes were analyzed to assess maturational status. After intra-implant or intraperitoneal injection with HIV-1, thymocytes were sorted by

Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I.

Two homosexual HIV-infected patients with lymphocyte counts of < 50 presented with intense pruritus, hyperpigmentation, and skin lesions clinically suggestive of the cutaneous T cell lymphoma, mycosis fungoides. On light microscopy, the skin biopsies were difficult to interpret because of the sparseness of the lymphocytic infiltrates. However, electron microscopy revealed typical Sézary cells in the peripheral blood and skin. Cultures of blood mononuclear cells of one of the patients generated HTLV-I-like particles. Although both patients lacked antibodies to HTLV, their blood and skin specime

Detection of human T-cell leukemia virus type I proviral sequences from fixed tissues of seropositive patients.

Fixed lymphoma tissues from 11 patients seropositive for human T-cell leukemia virus type I (HTLV-I) antibodies were analyzed for proviral sequences by the polymerase chain reaction. Typical adult T-cell leukemia/lymphomas (ATLLs) from nine patients were positive for HTLV-I sequences. In contrast, one of two lymphomas with immunophenotypes atypical for ATLL was negative for HTLV-I. This HTLV-I DNA-negative lymphoma, although present in an HTLV-I-seropositive patient, was therefore reclassified. The HTLV-I tax gene was always detected in the ATLL tissues, whereas segments of the pol gene were n

Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induc

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… In accordance with this, H3K9me3 and H3K27me3 accumulate on latent proviruses as the host cell—particularly host T cells—transitions to quiescence [ 61 ]. … Likewise, selective pressure from LT-ART results in a greater number of proviruses in heterochromatic regions in PWH [ 101 , 102 ]. …

Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts.

Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable H

Selective decline of intact HIV reservoirs during the first decade of ART followed by stabilization in memory T cell subsets.

OBJECTIVES: To investigate the short- and long-term dynamics of intact and defective proviral HIV DNA during ART. DESIGN: We evaluated viral reservoir dynamics in a cohort of nine individuals with chronic HIV-1 subtype B who initiated first-line ART and were followed for 20 years while continuing ART. METHODS: PBMCs were obtained before ART ( n  = 5), during the first year, and after 8.5 and 20 years of treatment. T cell subsets (naive, central-memory, transitional-memory and effector-memory) were sorted at 8.5 and 20 years. DNA was isolated and analyzed using the intact proviral DNA assay (

Screening for antibodies to human T-cell leukemia virus type I in Japanese breast milk.

Japanese breast milk samples were tested for antibodies to human T-cell leukemia virus type I (HTLV-1) by particle agglutination (PA) and a line immunoassay (LIA). In the PA method, the agglutination reaction between the HTLV-1 antibody and sensitized particles occurred at a 1 : 128 dilution of some breast milk samples. The average antibody titer was one order of magnitude lower than that in the serum positive control. A total of 243 human breast milk specimens were assayed by PA, of which 21 samples from Okinawa, Hyogo, Miyagi and Hokkaido were positive or deferred. The results of the 21 posi

Monitoring the HTLV-1 proviral load in the peripheral blood of asymptomatic carriers and patients with HTLV-associated myelopathy/tropical spastic paraparesis from a Brazilian cohort: ROC curve analysis to establish the threshold for risk disease.

Human T-lymphotropic virus 1 (HTLV-1) infection is associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which affects approximately 5% of carriers. High proviral load is a risk marker for HAM/TSP, although there is an overlap of proviral load levels in peripheral blood between asymptomatic carriers and HAM/TSP patients. In this study, receiver operating characteristic curve analysis was used to define a set point of HTLV-1 proviral load that better indicates an increased risk for HAM/TSP. Proviral load was quantified in 75 asymptomatic carriers and 78 HAM/TSP pati

Human T-lymphotropic virus type I (HTLV-I)-specific CD8+ cells accumulate in the lungs of patients infected with HTLV-I with pulmonary involvement.

Pulmonary involvement has been identified in human T-lymphotropic virus type I (HTLV-I) carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, the relationship between HTLV-I infection and lung disease is poorly understood. The occurrence of HTLV-I-specific immune responses in the lungs of patients infected with HTLV-I with pulmonary involvement was investigated. The frequency of HTLV-I-specific CD8+ cells and the amount of HTLV-I proviral DNA were determined in bronchoalveolar lavage fluid cells and peripheral blood mononuclear cells (PBMCs) f

Monotypic human immunodeficiency virus type 1 genotypes across the uterine cervix and in blood suggest proliferation of cells with provirus.

Understanding the dynamics and spread of human immunodeficiency virus type 1 (HIV-1) within the body, including within the female genital tract with its central role in heterosexual and peripartum transmission, has important implications for treatment and vaccine development. To study HIV-1 populations within tissues, we compared viruses from across the cervix to those in peripheral blood mononuclear cells (PBMC) during effective and failing antiretroviral therapy (ART) and in patients not receiving ART. Single-genome sequences of the C2-V5 region of HIV-1 env were derived from PBMC and three

Proviral load and immune markers associated with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru.

Human T-lymphotropic virus type 1 (HTLV-1) is the aetiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study is to identify which ex vivo and in vivo markers are associated independently with HAM/TSP in a Peruvian population. Eighty-one subjects (33 men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV-1 carriers (ACs) and 13 were HTLV-1-seronegative controls (SCs). Ex vivo markers included T cell proliferation and Th1 [interferon (IFN)-gamma], Th2 [interleukin (IL)-4, IL-5], proinflammatory [tumour necrosi

Natural controlled HIV infection: preserved HIV-specific immunity despite undetectable replication competent virus.

Long-term non-progressive HIV infection, characterized by low but detectable viral load and stable CD4 counts in the absence of antiviral therapy, is observed in about 5% of HIV-infected patients. Here we identified four therapy naïve individuals who are strongly seropositive for HIV-1 but who lack evidence of detectable HIV p24 antigen, plasma RNA, and proviral DNA in routine diagnostic testing. With an ultrasensitive PCR, we established that frequencies of pol proviral DNA sequences were as low as 0.2-0.5 copies/10(6) PBMC. HIV could not be isolated using up to 30x10(6) patient PBMC. One ind

Cutaneous granulomas associated with adult T-cell leukemia/lymphoma.

A 59-year-old Japanese woman showed recurrent violaceous, indurated erythemas and papules on the buttocks and extremities for a period of 7 years. The lesions showed histologically epithelioid cell granulomas associated with lymphocytes. After 7 years, the patient developed adult T-cell leukemia (ATL), of the acute type, the course of which was fatal. Immunohistochemical staining of the skin sections of granulomatous lesions showed prominent infiltration of CD25-positive cells. Human T-lymphotropic virus type I proviral DNA and monoclonal T-cell receptor beta gene rearrangement were detected i