Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Use Different Receptor Complexes To Enter T Cells

Jones, Kathryn; Fugo, Kazunori; Petrow‐Sadowski, Cari; Huang, Ying; Bertolette, Daniel C.; Lisinski, Ivonne; Cushman, Samuel W.; Jacobson, Steven; Ruscetti, Francis W.

doi:10.1128/jvi.00389-06

Cited by 71 publications

(89 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…by guest www.bloodjournal.org From are reported to be involved in HTLV-1 binding and entry, and are especially induced by stimulation. [23][24][25] Consistent with previous reports, all receptors were hardly or faintly expressed without activation but clearly induced on populations phenotypically identical to T SCM , T CM , and T EM after activation, except for GLUT1 24 (supplemental Figure 2A-C). The coculture assay of CD4 1 T cells with HTLV-1-producing cell line MT-2 illustrated that HTLV-1 was integrated to T SCM as well as T CM and T EM (supplemental Figure 3A-B), indicating that all the memory T-cell populations including T SCM have susceptibility to HTLV-1 infection.…”

supporting

confidence: 77%

T memory stem cells are the hierarchical apex of adult T-cell leukemia

Nagai

Kawahara

Hishizawa

et al. 2015

Blood

View full text Add to dashboard Cite

Key Points• ATL clones are preserved in a rare CD4 together, these findings demonstrate the phenotypic and functional heterogeneity and the hierarchy of ATL cells. T SCM cells are identified as the hierarchical apex capable of reconstituting identical ATL clones. Thus, this is the first report to demonstrate the association of a T-cell malignancy with T SCM cells. (Blood. 2015;125(23):3527-3535)

show abstract

supporting

confidence: 77%

T memory stem cells are the hierarchical apex of adult T-cell leukemia

Nagai

Kawahara

Hishizawa

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

“…It has been reported that CD8 ϩ T cells express much more GLUT1 than CD4 ϩ T cells (49,50). Nonetheless, HTLV-1 is found primarily in CD4 ϩ T cells in infected individuals (15).…”

Section: Discussionmentioning

confidence: 99%

Separate Cellular Localizations of Human T-Lymphotropic Virus 1 (HTLV-1) Env and Glucose Transporter Type 1 (GLUT1) Are Required for HTLV-1 Env-Mediated Fusion and Infection

Maeda

Terasawa

Tanaka

et al. 2015

J Virol

View full text Add to dashboard Cite

Interaction of the envelope glycoprotein (Env) of human T-lymphotropic virus 1 (HTLV-1) with the glucose transporter type 1 (GLUT1) expressed in target cells is essential for viral entry. This study found that the expression level of GLUT1 in virus-producing 293T cells was inversely correlated with HTLV-1 Env-mediated fusion activity and infectivity. Chimeric studies between GLUT1 and GLUT3 indicated that the extracellular loop 6 (ECL6) of GLUT1 is important for the inhibition of cell-cell fusion mediated by Env. When GLUT1 was translocated into the plasma membrane from intracellular storage sites by bafilomycin A1 (BFLA1) treatment in 293T cells, HTLV-1 Env-mediated cell fusion and infection also were inhibited without the overexpression of GLUT1, indicating that the localization of GLUT1 in intracellular compartments rather than in the plasma membrane is crucial for the fusion activity of HTLV-1 Env. Immunoprecipitation and laser scanning confocal microscopic analyses indicated that under normal conditions, HTLV-1 Env and GLUT1 do not colocalize or interact. BFLA1 treatment induced this colocalization and interaction, indicating that GLUT1 normally accumulates in intracellular compartments separate from that of Env. Western blot analyses of FLAGtagged HTLV-1 Env in virus-producing cells and the incorporation of HTLV-1 Env in virus-like particles (VLPs) indicate that the processing of Env is inhibited by either overexpression of GLUT1 or BFLA1 treatment in virus-producing 293T cells. This inhibition probably is due to the interaction of the Env with GLUT1 in intracellular compartments. Taken together, separate intracellular localizations of GLUT1 and HTLV-1 Env are required for the fusion activity and infectivity of HTLV-1 Env. IMPORTANCEThe deltaretrovirus HTLV-1 is a causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although HTLV-1 is a complex retrovirus that has accessory genes, no HTLV-1 gene product has yet been shown to regulate its receptor GLUT1 in virus-producing cells. In this study, we found that a large amount of GLUT1 or translocation of GLUT1 to the plasma membrane from intracellular compartments in virus-producing cells enhances the colocalization and interaction of GLUT1 with HTLV-1 Env, leading to the inhibition of cell fusion activity and infectivity. The results of our study suggest that GLUT1 normally accumulates in separate intracellular compartments from Env, which is indeed required for the proper processing of Env. Human T-lymphotropic virus 1 (HTLV-1) is a complex deltaretrovirus and a causative agent of adult T-cell leukemia (ATL) (62-64) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (1, 2). The envelope glycoprotein (Env) of HTLV-1 is synthesized in virus-infected cells as a polyprotein precursor (gp62), which subsequently is cleaved by cellular proteinase(s) localized in the Golgi apparatus into two proteins, surface glycoprotein (gp46; SU) and transmembrane glycoprotein (gp21; TM...

show abstract

“…Notably, we find that binding to the BLV receptor did not require the presence of immediately downstream PRR sequences of BLV Env. This is of particular importance since, in the context of HTLV, retroviral PRR or downstream sequences may bind to cell surface components other than the primary receptor (45,46), and sequences outside the RBD in some gammaretrovirus SU appear to modulate or block binding and infection (47)(48)(49). Nevertheless, in the context of the BLV envelope, an Env-specific binding interference assay demonstrated that the BLV RBD alone decreased B RBD binding to levels similar to that detected in the presence of the entire BLV Env.…”

Section: Discussionmentioning

confidence: 99%

Cell Surface Expression of the Bovine Leukemia Virus-Binding Receptor on B and T Lymphocytes Is Induced by Receptor Engagement

Lavanya

Kinet

Montel‐Hagen

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Bovine leukemia virus (BLV), one of the most common infectious viruses of cattle, is endemic in many herds. Approximately 30–40% of adult cows in the United States are infected by this oncogenic C-type retrovirus and 1–5% of animals will eventually develop a malignant lymphoma. BLV, like the human and simian T cell leukemia viruses, is a deltaretrovirus but, in contrast with the latter, the BLV receptor remains unidentified. In this study, we demonstrate that the amino-terminal 182 residues of the BLV envelope glycoprotein surface unit encompasses the receptor-binding domain. A bona fide interaction of this receptor-binding domain with the BLV receptor was demonstrated by specific interference with BLV, but not human T cell leukemia virus, envelope glycoprotein-mediated binding. We generated a rabbit Ig Fc-tagged BLV receptor-binding domain construct and ascertained that the ligand binds the BLV receptor on target cells from multiple species. Using this tool, we determined that the BLV-binding receptor is expressed on differentiating pro/pre-B cells in mouse bone marrow. However, the receptor was not detected on mature/quiescent B cells but was induced upon B cell activation. Activation of human B and T lymphocytes also induced surface BLV-binding receptor expression and required de novo protein synthesis. Receptor levels were down-regulated as activated lymphocytes returned to quiescence. In the human thymus, BLV-binding receptor expression was specifically detected on thymocytes responding to the IL-7 cytokine. Thus, expression of the BLV-binding receptor is a marker of enhanced metabolic activity in B cells, T cells, and thymocytes.

show abstract

Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Use Different Receptor Complexes To Enter T Cells

Cited by 71 publications

References 58 publications

T memory stem cells are the hierarchical apex of adult T-cell leukemia

T memory stem cells are the hierarchical apex of adult T-cell leukemia

Separate Cellular Localizations of Human T-Lymphotropic Virus 1 (HTLV-1) Env and Glucose Transporter Type 1 (GLUT1) Are Required for HTLV-1 Env-Mediated Fusion and Infection

Cell Surface Expression of the Bovine Leukemia Virus-Binding Receptor on B and T Lymphocytes Is Induced by Receptor Engagement

Contact Info

Product

Resources

About