Результаты поиска

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 5: Strategies to prevent transmission of porcine endogenous retroviruses.

Xenotransplantation using porcine cells, tissues, or organs may offer a potential solution for the shortage of allogeneic human organs. Prio … infect human cells; (ii) are characterized by high titre replication; and (iii) are associated with proviruses that are de novo integrated in the DNA of somatic pig cells, but not yet in the pig germ line. The risks presented by PERV-A/C recombinant viruses could easily be eliminated by using pigs not containing PERV-C in their germ line, thereby effectively …

Lost in transcription: molecular mechanisms that control HIV latency.

Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover,

Совпадение в полном тексте источника
… Low levels of basal transcription factors, NFκB and NFAT, further restrict HIV transcription initiation, and ensure that latent proviruses remain transcriptionally silenced for long periods of time [ 88 , 89 , 90 , 91 ]. … Vorinostat could become a component of the “shock and kill” approach, where a “shock” phase reactivates latent proviruses then a “kill” step limits viral replication and spread with HAART [ 183 ]. …

Evaluation of the Association of Cytokines, Interleukin 6 Polymorphism, and Proviral Load With Myelopathy, Pain, and Functionality in HTLV1-Infected Patients.

The factors involved in the development of functional dependence, pain and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) could be linked to inflammatory cytokines and proviral load. This study aimed to assess the association between myelopathy, pain, and functionality with proviral load in blood, serum levels of cytokines and the interleukin 6 (IL-6) polymorphism in individuals living with HTLV-1. This was a cross-sectional study. Consecutive HTLV-1-infected patients, with or without HAM/TSP, attending the infectious diseases clinic were included. A semi-structured questi

Complete remission and proviral load negativization after allogeneic-SCT in a patient with Adult T-cell lymphoma: Case report.

Adult T-cell lymphoma is an aggressive and poor prognosis HTLV1-associated lymphoma. There is no standard treatment, but it is known that intensive chemotherapy regimens are necessary, with or without concomitant antiretroviral therapy, plus consolidation with allogeneic stem cell transplantation. Our case report shows a favorable outcome after 2 cycles of chemotherapy and allogeneic stem cell transplantation without antiretroviral agents, achieving complete remission, and a negative proviral load.

Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results.

Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cell

HTLV-1 drives vigorous clonal expansion of infected CD8(+) T cells in natural infection.

BACKGROUND: Human T-lymphotropic Virus Type I (HTLV-1) is a retrovirus that persistently infects 5-10 million individuals worldwide and causes disabling or fatal inflammatory and malignant diseases. The majority of the HTLV-1 proviral load is found in CD4(+) T cells, and the phenotype of adult T cell leukemia (ATL) is typically CD4(+). HTLV-1 also infects CD8(+) cells in vivo, but the relative abundance and clonal composition of the two infected subpopulations have not been studied. We used a high-throughput DNA sequencing protocol to map and quantify HTLV-1 proviral integration sites in separ

Low Proviral Load is Associated with Indeterminate Western Blot Patterns in Human T-Cell Lymphotropic Virus Type 1 Infected Individuals: Could Punctual Mutations be Related?

BACKGROUND: indeterminate Western blot (WB) patterns are a major concern for diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) infection, even in non-endemic areas. OBJECTIVES: (a) to define the prevalence of indeterminate WB among different populations from Argentina; (b) to evaluate if low proviral load (PVL) is associated with indeterminate WB profiles; and (c) to describe mutations in LTR and tax sequence of these cases. RESULTS: Among 2031 samples, 294 were reactive by screening. Of them, 48 (16.3%) were WB indeterminate and of those 15 (31.3%) were PCR+. Quantitative real-ti

Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers.

Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRN

Development of peripheral T-cell lymphoma not otherwise specified in an HTLV-1 carrier.

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) after a long latency period of about 60 years. As the mature T-cell neoplasms that emerge in patients infected with HTLV-1 are often ATL, T-cell neoplasms developing in such patients tend to be diagnosed simply as ATL without further investigation. However, not all T-cell neoplasms that develop in HTLV-1-infected cases are ATL. Mature T-cell malignancies other than ATL should be carefully excluded in patients infected with HTLV-1, as these sometimes closely resemble ATL in their clinical, morphological, and histolog

Heme arginate potentiates latent HIV-1 reactivation while inhibiting the acute infection.

Human immunodeficiency virus-1 (HIV-1) successfully escapes from host immune surveillance, vaccines and antiretroviral agents. The available antiretroviral compounds can only control viremia, but it is impossible to eliminate the virus from the organism, namely because HIV-1 provirus persists in the reservoir cells from which the virus repeatedly disseminates into new cells. Current therapeutic approaches, however, do not specifically address the stage of virus reactivation. Heme has been demonstrated as very efficient in inhibiting HIV-1 reverse transcription, while its derivative hemin ameli

Characterization and frequency of a newly identified HIV-1 BF1 intersubtype circulating recombinant form in São Paulo, Brazil.

BACKGROUND: HIV circulating recombinant forms (CRFs) play an important role in the global and regional HIV epidemics, particularly in regions where multiple subtypes are circulating. To date, several (>40) CRFs are recognized worldwide with five currently circulating in Brazil. Here, we report the characterization of near full-length genome sequences (NFLG) of six phylogenetically related HIV-1 BF1 intersubtype recombinants (five from this study and one from other published sequences) representing CRF46_BF1. METHODS: Initially, we selected 36 samples from 888 adult patients residing in São Pa

HIV-1 infection of monocytes is directly related to the success of HAART.

Macrophages are recognized cellular compartments involved in HIV infection; however, the extent to which precursor monocytes are infected in vivo and its significance remains poorly understood. Our aim was to analyze the contribution of monocytes to HIV infection in vivo. PCR assays did not detect HIV-1 proviral DNA in monocytes of HAART-suppressed patients. Monocyte-derived macrophages from individuals under suppressive HAART did not show evidence of harboring HIV, thereby, minimizing the possibility of infection by the integration of sequestered virus after differentiation. These results sug

Reduction of human T-cell leukemia virus type 1 (HTLV-1) proviral loads in rats orally infected with HTLV-1 by reimmunization with HTLV-1-infected cells.

Human T-cell leukemia virus type 1 (HTLV-1) persistently infects humans, and the proviral loads that persist in vivo vary widely among individuals. Elevation in the proviral load is associated with serious HTLV-1-mediated diseases, such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, it remains controversial whether HTLV-1-specific T-cell immunity can control HTLV-1 in vivo. We previously reported that orally HTLV-1-infected rats showed insufficient HTLV-1-specific T-cell immunity that coincided with elevated levels of the HTLV-1 proviral load.

The clonal expansion of human T lymphotropic virus type 1-infected T cells: a comparison between seroconverters and long-term carriers.

BACKGROUND: The clonal expansion of human T lymphotropic virus type 1 (HTLV-1)-infected T cells is considered to be important for the maintenance of infection. However, the process by which the clonality of HTLV-1-infected T cells is established is not understood. METHODS: HTLV-1 clonality in 4 adult seroconverters was analyzed by inverse long polymerase chain reaction (PCR) followed by cloning of the PCR products and evaluation of restriction fragment-length polymorphism. The results were compared with those for 8 long-term HTLV-1 carriers. RESULTS: The clonality of HTLV-1-infected T cells

Virus burden in lymph nodes and blood of subjects with primary human immunodeficiency virus type 1 infection on bitherapy.

At present, it is not known whether undetectable plasma viremia corresponds to an absence of human immunodeficiency virus type 1 (HIV-1) replication in lymphoid tissues. This issue has been explored in 11 subjects with primary HIV-1 infection treated with zidovudine plus didanosine by evaluating virologic markers in blood and lymphoid tissues 9-18 months after initiation of treatment. These markers include plasma viremia, measured with a sensitive assay with a detection limit of 20 HIV-1 RNA copies/mL, infectious virus titers and proviral DNA in lymph node mononuclear cells, and HIV-1 RNA in l

Determination of human T lymphotropic virus type by polymerase chain reaction and correlation with risk factors in northern California blood donors.

To determine the relative prevalence of human T lymphotropic virus (HTLV) types I and II, type-specific polymerase chain reaction (PCR) was done on seropositive northern California blood donors. From October 1988 through March 1990, 67 (0.055%) of 122,517 blood donors had confirmed HTLV antibody. Seropositive donors were more likely to be middle-aged, female, and nonwhite than the overall donor base. PCR of samples from 30 HTLV-seropositive donors yielded 19 (63%) with HTLV-II and 9 (30%) with HTLV-I; 2 (7%) were repeatedly negative by PCR. HTLV-I-infected subjects had ancestry (n = 3), sexual

Human immunodeficiency virus type 1 (HIV-1) infection a median of 18 months before a diagnostic western blot. Evidence from a cohort of homosexual men.

STUDY OBJECTIVE: To study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, we used an in-vitro amplification technique to detect HIV-1 nucleic acid sequences in sequential aliquots of peripheral blood mononuclear cells from homosexual men enrolled in the Multicenter AIDS Cohort Study. DESIGN AND PATIENTS: Blinded, longitudinal study of 24 homosexual men who were positive for HIV-1 antibodies at a recent follow-up visit. MEASUREMENTS AND MAIN RESULTS: Coded clinical samples were evaluated using two enzyme-linked immunosorbent assays (whole virus and gp120-gp41 fra

Inhibition of ABL1 tyrosine kinase reduces HTLV-1 proviral loads in peripheral blood mononuclear cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellular genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP patients and found that the ABL1 is an important gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes and is part of the fused gene (BCR-ABL) known to be responsi

Oral health profile in patients infected with HTLV-1: clinical findings, proviral load, and molecular analysis from HTLV-1 in saliva.

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been implicated in several disorders, including periodontal disease. The proviral load is an important biological marker for understanding HTLV-1 pathogenesis and elucidating whether or not the virus is related to the clinical manifestation of the disease. This study describes the oral health profile of HTLV-1 carriers and HAM/TSP patients in order to investigate the association between the proviral load in saliva and the

Infection, viral dissemination, and antibody responses of rhesus macaques exposed to the human gammaretrovirus XMRV.

Xenotropic murine leukemia-related virus (XMRV) was identified in association with human prostate cancer and chronic fatigue syndrome. To examine the infection potential, kinetics, and tissue distribution of XMRV in an animal model, we inoculated five macaques with XMRV intravenously. XMRV established a persistent, chronic disseminated infection, with low transient viremia and provirus in blood lymphocytes during acute infection. Although undetectable in blood after about a month, XMRV viremia was reactivated at 9 months, confirming the chronicity of the infection. Furthermore, XMRV Gag was de