HTLV envelopes and their receptor GLUT1, the ubiquitous glucose transporter: a new vision on HTLV infection?

Manel, Nicolas; Taylor, Naomi; Kinet, Sandrina; Kim, Felix J.; Swainson, Louise; Lavanya, Madakasira; Battini, Jean-Luc; Sitbon, Marc

doi:10.2741/1474

Cited by 16 publications

(11 citation statements)

References 189 publications

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“…However, the observation by our laboratory and others that HTLV-1 SU binds primarily to HSPGs (19,39) is at odds with other studies that stated that both HTLV-1 and HTLV-2 SU bind directly to GLUT-1 (21,22,29). These latter studies also stated that the N-terminal 215 amino acids of the HTLV SU (RBD region) contain all the sequences needed for optimal binding.…”

Section: Discussioncontrasting

confidence: 55%

“…Studies of the organization of Env proteins of gammaretroviruses have shown that SU proteins consist of an N-terminal region which binds directly to the receptor (the receptor binding domain, or RBD), a short proline-rich "hinge" region (PRR), and a C-terminal region critical for fusion (1,4,5,20,24,35). Later studies suggested that HTLV SU has a similar modular structure (21,22,29). Based on this organization, we generated four recombinants between HTLV-1 and HTLV-2 SU, producing chimeric proteins (Fig.…”

Section: Differences In Htlv-1 and Htlv-2 Binding To Cd4mentioning

confidence: 99%

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

Jones

Fugo

Petrow‐Sadowski

et al. 2006

J Virol

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Studies using adherent cell lines have shown that glucose transporter-1 (GLUT-1) can function as a receptor for human T-cell leukemia virus type 1 (HTLV). In primary CD4؉ T cells, heparan sulfate proteoglycans (HSPGs) are required for efficient entry of HTLV-1. Here, the roles of HSPGs and GLUT-1 in HTLV-1 and HTLV-2 Env-mediated binding and entry into primary T cells were studied. Examination of the cell surface of activated primary T cells revealed that CD4 ؉ T cells, the primary target of HTLV-1, expressed significantly higher levels of HSPGs than CD8 ؉ T cells. Conversely, CD8 ؉ T cells, the primary target of HTLV-2, expressed GLUT-1 at dramatically higher levels than CD4 ؉ T cells. Under these conditions, the HTLV-2 surface glycoprotein (SU) binding and viral entry were markedly higher on CD8؉ T cells while HTLV-1 SU binding and viral entry were higher on CD4 ؉ T cells. Binding studies with HTLV-1/HTLV-2 SU recombinants showed that preferential binding to CD4 ؉ T cells expressing high levels of HSPGs mapped to the C-terminal portion of SU. Transfection studies revealed that overexpression of GLUT-1 in CD4 ؉ T cells increased HTLV-2 entry, while expression of HSPGs on CD8 ؉ T cells increased entry of HTLV-1. These studies demonstrate that HTLV-1 and HTLV-2 differ in their T-cell entry requirements and suggest that the differences in the in vitro cellular tropism for transformation and in vivo pathobiology of these viruses reflect different interactions between their Env proteins and molecules on CD4؉ and CD8 ؉ T cells involved in entry.Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) are deltaretroviruses with similar genome structure and an overall nucleotide homology of approximately 70% (reviewed in reference 11). However, the two viruses differ in their pathobiology. HTLV-1 is the causal agent of adult T-cell leukemia and a progressive neurological disorder called HTLV-1-associated myelopathy/tropical spastic paraparesis (12,34,54). In contrast, HTLV-2 is essentially nonpathogenic, although a few cases of neurological disease in HTLV-2-infected individuals have been reported.Entry of retroviruses into target cells involves interactions between the viral envelope (Env) glycoproteins, a surface glycoprotein (SU), and a transmembrane glycoprotein (TM), and specific cell surface molecules referred to as receptors. The SU protein is involved in receptor recognition, and the TM protein triggers the fusion of the viral and cellular membranes, allowing entry of viral particles. For some retroviruses such as ecotropic murine leukemia viruses, a single molecule is sufficient for attachment and entry; for others such as human immunodeficiency virus (HIV), multiple molecules are required (37).Studies of viral interference indicate that HTLV-1, HTLV-2, and related simian viruses share a receptor (46,47). Cells from a variety of species express molecules capable of supporting HTLV-1 Env-mediated fusion. Many, but not all, cell lines can be transduced by HTLV-1 Env-pseudotyped vectors and/or can fuse wit...

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Section: Discussioncontrasting

confidence: 55%

Section: Differences In Htlv-1 and Htlv-2 Binding To Cd4mentioning

confidence: 99%

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

Jones

Fugo

Petrow‐Sadowski

et al. 2006

J Virol

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“…Further investigation of the underlying mechanisms utilized by HTLV Env will be a most worthy pursuit. To date, many cellular factors have been implicated in Env-mediated HTLV infection and syncytium formation, including heat shock protein (HSP-70), various adhesion molecules (VCAM-1 and ICAM-1), membrane glycoprotein C33, HLA A2 receptor, IL-2 receptor, lipid rafts, and the glucose transporter GLUT-1 (9,12,20,27,39,45,47,64,72). The failure to identify a conclusive receptor for HTLV suggests that more than one cell surface molecule may play a critical role in HTLV entry.…”

Section: Discussionmentioning

confidence: 99%

Envelope Is a Major Viral Determinant of the Distinct In Vitro Cellular Transformation Tropism of Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2

Xie¹,

Green

2005

J Virol

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Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are related deltaretroviruses but are distinct in their disease-inducing capacity. These viruses can infect a variety of cell types, but only T lymphocytes become transformed, which is defined in vitro as showing indefinite interleukin-2-independent growth. Studies have indicated that HTLV-1 has a preferential tropism for CD4 ؉ T cells in vivo and is associated with the development of leukemia and neurological disease. Conversely, the in vivo T-cell tropism of HTLV-2 is less clear, although it appears that CD8 ؉ T cells preferentially harbor the provirus, with only a few cases of disease association. The difference in T-cell transformation tropism has been confirmed in vitro as shown by the preferential transformation of CD4 ؉ T cells by HTLV-1 versus the transformation of CD8 ؉ T cells by HTLV-2. Our previous studies showed that Tax and overlapping Rex do not confer the distinct T-cell transformation tropisms between HTLV-1 and HTLV-2. Therefore, for this study HTLV-1 and HTLV-2 recombinants were generated to assess the contribution of LTR and env sequences in T-cell transformation tropism. Both sets of proviral recombinants expressed p19 Gag following transfection into cells. Furthermore, recombinant viruses were replication competent and had the capacity to transform T lymphocytes. Our data showed that exchange of the env gene resulted in altered T-cell transformation tropism compared to wild-type virus, while exchange of long terminal repeat sequences had no significant effect. HTLV-2/Env1 preferentially transformed CD4 ؉ T cells similarly to wild-type HTLV-1 (wtHTLV-1), whereas HTLV-1/Env2 had a transformation tropism similar to that of wtHTLV-2 (CD8 ؉ T cells). These results indicate that env is a major viral determinant for HTLV T-cell transformation tropism in vitro and provides strong evidence implicating its contribution to the distinct pathogenesis resulting from HTLV-1 versus HTLV-2 infections.

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“…The interest of our groups in this domain was motivated, at least in part, by our identification of the Glut1 glucose transporter as the human T-cell leukemia virus (HTLV) receptor ( [14,[22][23][24]. Notably, cell surface up-regulation of metabolite transporters is a rate-limiting step for nutrient uptake following cell stimulation.…”

Section: Text Of Reviewmentioning

confidence: 98%

Metabolic pathways as regulators of HIV infection

Craveiro

Clerc

Sitbon

et al. 2013

Current Opinion in HIV and AIDS

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HTLV envelopes and their receptor GLUT1, the ubiquitous glucose transporter: a new vision on HTLV infection?

Cited by 16 publications

References 189 publications

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

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

Envelope Is a Major Viral Determinant of the Distinct In Vitro Cellular Transformation Tropism of Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2

Metabolic pathways as regulators of HIV infection

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