Regulation of Expression and Latency in BLV and HTLV.

(HTLV-1) and (BLV) belong to the genus. HTLV-1 is the etiologic agent of the highly aggressive and currently incurable cancer adult T-cell leukemia (ATL) and a neurological disease HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). BLV causes neoplastic proliferation of B cells in cattle: enzootic bovine leucosis (EBL).

A novel positive feedback-loop between the HTLV-1 oncoprotein Tax and NF-κB activity in T-cells.

Background: Human T-cell leukemia virus type 1 (HTLV-1) infects primarily CD4 T-lymphocytes and evoques severe diseases, predominantly Adult T-Cell Leukemia/ Lymphoma (ATL/L) and HTLV-1-associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP). The viral transactivator of the pX region (Tax) is important for initiating malignant transformation, and deregulation of the major signaling pathway nuclear factor of kappa B (NF-κB) by Tax represents a hallmark of HTLV-1 driven cancer.

Results: Here we found that Tax mutants which are defective in NF-κB signaling showed diminished protein expression levels compared to Tax wildtype in T-cells, whereas Tax transcript levels were comparable.

RNF8 Dysregulation and Down-regulation During HTLV-1 Infection Promote Genomic Instability in Adult T-Cell Leukemia.

The genomic instability associated with adult T cell leukemia/lymphoma (ATL) is causally linked to Tax, the HTLV-1 viral oncoprotein, but the underlying mechanism is not fully understood. We have previously shown that Tax hijacks and aberrantly activates ring finger protein 8 (RNF8) - a lysine 63 (K63)-specific ubiquitin E3 ligase critical for DNA double-strand break (DSB) repair signaling - to assemble K63-linked polyubiquitin chains (K63-pUbs) in the cytosol. Tax and the cytosolic K63-pUbs, in turn, initiate additional recruitment of linear ubiquitin assembly complex (LUBAC) to produce hybrid K63-M1 pUbs, which trigger a kinase cascade that leads to canonical IKK:NF-κB activation.

Clinical Characteristics of Disseminated Strongyloidiasis, Japan, 1975-2017.

Clinical characteristics of disseminated strongyloidiasis, the severest form of strongyloidiasis, are not well described. We conducted a retrospective, consecutive chart review of patients with disseminated strongyloidiasis admitted to Okinawa Chubu Hospital in Okinawa, Japan, during January 1975-December 2017. The 70 patients were classified into 3 clinical phenotypes: dissemination (32 patients [45.

Idiopathic CD4+ T lymphocytopenia: A case report.

Idiopathic CD4+ T lymphocytopenia (ICL) is a very rare immunodeficiency syndrome with an unexplained depletion of CD4+ T lymphocytes and no evidence of Human Immunodeficiency Virus (HIV) infection. Here we report a 29-year-old male patient who had severe ulcerative colitis with low level CD4+ count of 254 cells/mm, and had no evidence of HIV or Human T cell Lymphotrophic virus type I or II infections. He had recurrent Candidiasis infection and his CD4 count was just 53 cells/mm after 3 months.

EOS, an Ikaros family zinc finger transcription factor, interacts with the HTLV-1 oncoprotein Tax and is downregulated in peripheral blood mononuclear cells of HTLV-1-infected individuals, irrespective of clinical statuses.

Background: EOS plays an important role in maintaining the suppressive function of regulatory T cells (Tregs), and induces a regulated transformation of Tregs into T helper-like cells, which are capable of secreting proinflammatory cytokines in response to specific inflammatory signals. Meanwhile, significant reduction in Treg activity along with production of proinflammatory cytokines has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Methods: In this study, to examine whether there is an alteration in EOS expression in peripheral blood mononuclear cells (PBMCs) derived from HTLV-1-infected individuals especially HAM/TSP, we investigated the expression of HTLV-1 tax genotype, proviral load (PVL), and the mRNA expression of tax, HBZ and EOS in HTLV-1 infected individuals including adult T-cell leukemia/lymphoma (ATL), HAM/TSP, or asymptomatic carriers.

SQSTM-1/p62 potentiates HTLV-1 Tax-mediated NF-κB activation through its ubiquitin binding function.

The NF-κB pathway is constitutively activated in adult T cell leukemia, an aggressive malignancy caused by Human T Leukemia Virus type 1 (HTLV-1). The viral oncoprotein Tax triggers this constitutive activation by interacting with the ubiquitin-rich IKK complex. We previously demonstrated that Optineurin and TAX1BP1, two members of the ubiquitin-binding, Sequestosome-1 (SQSTM-1/p62)-like selective autophagy receptor family, are involved in Tax-mediated NF-κB signaling.

The ESCRT-0 Protein HRS Interacts with the Human T Cell Leukemia Virus Type 2 Antisense Protein APH-2 and Suppresses Viral Replication.

The divergent clinical outcomes of human T cell leukemia virus type 1 (HTLV-1) and HTLV-2 infections have been attributed to functional differences in their antisense proteins. In contrast to HTLV-1 bZIP factor (HBZ), the role of the antisense protein of HTLV-2 (APH-2) in HTLV-2 infection is poorly understood. In previous studies, we identified the endosomal sorting complex required for transport 0 (ESCRT-0) subunit HRS as a novel interaction partner of APH-2 but not HBZ.

Flow cytometric methodology for the detection of de novo human T-cell leukemia virus -1 infection in vitro: A tool to study novel infection inhibitors.

Methodology to detect and study de novo human T-cell leukemia virus (HTLV)-1 infection is required to further our knowledge of the viruses' mechanisms of infection and to study potential therapeutic interventions. Whilst methodology currently exists, utilisation of an anti-Tax antibody to detect de novo Tax expression in permissive cells labelled with cell tracker allowing for the detection by flow cytometry of new infection after co-culture with donor cell lines productively infected with HTLV-1 is an alternative strategy. Using this methodology, we have been able to detect de novo infection of the T cell line HUT78 following co-culture with the productively infected HTLV-1 donor cell line MT-2 and to confirm that infection can be effectively blocked with well characterised infection inhibitors.

Early and Successful Combination Antiretroviral Therapy Normalizes Survival Time in Patients Coinfected With Human Immunodeficiency Virus and Human T-cell Lymphotrophic Virus Type 1.

Background: Coinfection with human T-cell lymphotrophic virus type 1 (HTLV-1) is associated with shorter survival for adults and children infected with human immunodeficiency virus (HIV), although the reasons remain a matter of debate. We evaluated the factors associated with survival time in a large cohort of HIV/HTLV-1-coinfected and HIV-monoinfected individuals on combination antiretroviral therapy (cART).

Methods: In a nested, retrospective case-control study (1:1), we reviewed medical records of people with HIV infection on cART in a referral AIDS center in Salvador, Brazil.

The human T-cell leukemia virus type-1 tax oncoprotein dissociates NF-κB p65-Stathmin complexes and causes catastrophic mitotic spindle damage and genomic instability.

Genomic instability is a hallmark of many cancers; however, the molecular etiology of chromosomal dysregulation is not well understood. The human T-cell leukemia virus type-1 (HTLV-1) oncoprotein Tax activates NF-κB-signaling and induces DNA-damage and aberrant chromosomal segregation through diverse mechanisms which contribute to viral carcinogenesis. Intriguingly, Stathmin/oncoprotein-18 (Op-18) depolymerizes tubulin and interacts with the p65 subunit and functions as a cofactor for NF-κB-dependent transactivation.

HTLV-1 basic leucine zipper factor protects cells from oxidative stress by upregulating expression of Heme Oxygenase I.

Adult T-cell Leukemia (ATL) is a lymphoproliferative disease of CD4+ T-cells infected with Human T-cell Leukemia Virus type I (HTLV-1). With the exception of allogeneic hematopoietic stem cell transplantation, there are no effective treatments to cure ATL, and ATL cells often acquire resistance to conventional chemotherapeutic agents. Accumulating evidence shows that development and maintenance of ATL requires key contributions from the viral protein, HTLV-1 basic leucine zipper factor (HBZ).

Novel Interactions between the Human T-Cell Leukemia Virus Type 1 Antisense Protein HBZ and the SWI/SNF Chromatin Remodeling Family: Implications for Viral Life Cycle.

The human T-cell leukemia virus type 1 (HTLV-1) regulatory proteins Tax and HBZ play indispensable roles in regulating viral and cellular gene expression. BRG1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, has been demonstrated to be essential not only for Tax transactivation but also for viral replication. We sought to investigate the physical interaction between HBZ and BRG1 and to determine the effect of these interactions on Tax-mediated long terminal repeat (LTR) activation.

HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1.

An estimated 10-20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle.

Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB.

Cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is identified as a novel cell surface marker for human T-cell leukemia virus (HTLV-1)-infected T cells. Adult T-cell leukemia/lymphoma (ATLL) is developed in HTLV-1-infected T-cells after a long infection period. To examine the mechanism of CADM1 overexpression in ATLL, we first identified that CADM1 is transcriptionally up-regulated by a transcriptional enhancer element through NF-κB signaling pathway.

[Primary cutaneous localization revealing leukemia/T-cell lymphoma associated with chronic HTLV-1 infection in a adult. A case presentation].

Adult T-cell leukemia/lymphoma (ATLL) is a rare medical condition and a diagnosis that ought to be considered for patients living in an area endemic for the HTLV-1 virus (human T-lymphotrophic virus) where a T-cell lymphoproliferative diagnosis has been made. The cutaneous clinical forms may be the first manifestation of the disease. We report here an observation in a 60-year-old Senegalese woman whose skin lesions were sampled to reveal the ATLL immunophenotypic profile CD4+, CD25+, FoxP3-, and CD7-.

Diversity of cell phenotypes among MT-2 cell lines affects the growth of U937 cells and cytokine production.

We previously reported the diversity of structure and integration sites of human T-cell leukemia virus type 1 (HTLV-1) provirus among different MT-2 cell lines. This raised the question as to whether cell phenotypes also differed among MT-2 cell lines. The influence of two different MT-2 cell lines (MT-2J and MT-2B) on the growth of the promonocytic leukemia cell line, U937, was investigated.