In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II).

Ijichi, Shinji; Ramundo, Mary B.; Takahashi, Hitomi; Hall, William W.

doi:10.1084/jem.176.1.293

Cited by 103 publications

(46 citation statements)

References 25 publications

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“…While HTLV-1 has a preferential tropism for CD4 + T cells in both asymptomatic patients and those with neurological disease (162), the in vivo tropism of HTLV-2 is less clear. Some reports indicate that it can be detected in both CD4 + CD8 + T cells, with greater viral burden in CD8 + T-cells (162)(163)(164)(165). In vitro, HTLV-2 has a preferential tropism for CD8 + T cells (166,167).…”

Section: The Role Of Rex In Cellular Transformation Viral Spread Anmentioning

confidence: 99%

The Human T-cell leukemia virus Rex protein

Ihab¹

2005

Front Biosci

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A critical step in the life cycle of complex retroviruses, including HTLV-1 and HTLV-2 is the ability of these viruses to adopt a mechanism by which the genome-length unspliced mRNA as well as the partially spliced mRNAs are exported from the nucleus instead of being subjected to splicing or degradation. In HTLV, this is accomplished through the expression of the viral Rex, which recognizes a specific response element on the incompletely spliced mRNAs, stabilizes them, inhibits their splicing, and utilizes the CRM1-dependent cellular pathway for transporting them from the nucleus to the cytoplasm. Rex itself is regulated by phosphorylation, which implies that proper activation of the protein in response to certain cellular cues is an important tool for the virus to ensure that specific viral gene expression is allowed only when the host cell can provide the best conditions for virion production. Having such a critical role in HTLV life cycle, Rex is indispensable for efficient viral replication, infection and spread. Indeed, Rex is considered to regulate the switch between the latent and productive phases of the HTLV life cycle. Without a functional Rex, the virus would still produce regulatory and some accessory gene products; however, structural and enzymatic post-transcriptional gene expression would be severely repressed, essentially leading to non-productive viral replication. More detailed understanding of the exact molecular mechanism of action of Rex will thus allow for better design of therapeutic drugs against Rex function and ultimately HTLV replication. Herein we summarize the progress made towards understanding Rex function and its role in the HTLV life cycle.

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Section: The Role Of Rex In Cellular Transformation Viral Spread Anmentioning

confidence: 99%

The Human T-cell leukemia virus Rex protein

Ihab¹

2005

Front Biosci

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“…ϩ T cells in vivo (11,12). Both HTLV-I and HTLV-II can infect all human lymphocytic subsets, causing polyclonal and monoclonal T cell lymphocytoses (reviewed in Ref.…”

Section: Induction Of Human T Cell Leukemia Virus Type I Receptors Onmentioning

confidence: 99%

Induction of Human T Cell Leukemia Virus Type I Receptors on Quiescent Naive T Lymphocytes by TGF-β

Jones

Akel

Petrow‐Sadowski

et al. 2005

The Journal of Immunology

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The retrovirus human T cell leukemia virus (HTLV) type I (HTLV-I) is primarily transmitted by breast-feeding or sexual contact, by cell-to-cell contact between T cells. TGF-β, which has been shown to enhance transmission of HTLV-I in vitro, is found at high levels in breast milk and semen. In this study, the ability of TGF-β to regulate expression of molecules involved in HTLV-I binding and entry was examined. Previous studies using a soluble form of the HTLV-I envelope protein SU have shown that quiescent human T cells do not express cell surface molecules that specifically bind SU. After T cell activation, HTLV SU binding proteins are rapidly induced. In this study, we report that TGF-β induces expression of proteins that bind soluble HTLV SU and HTLV virions on naive CD4+ T lymphocytes. The induction of these proteins occurred without cell cycle entry or expression of activation markers, involved TGF-β-induced intracellular signaling, and required de novo transcription and translation. Treatment of naive CD4+ T lymphocytes with TGF-β induced expression of GLUT-1, which has recently been reported to function as a receptor for HTLV. Treatment of a TGF-β-sensitive human myeloid cell line increased the titer of both HTLV-I- and HTLV-II-pseudotyped viruses. Although earlier studies suggested that HTLV SU binding proteins might be an early marker of T cell activation and/or cell proliferation, we report in this study that TGF-β induces binding of HTLV virions and expression of glucose transporter type 1 in primary CD4+ T lymphocytes that remain quiescent.

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“…Activated CD4 ϩ T cells express much higher levels of HSPGs than CD8 ϩ T cells (26). In infected individuals, HTLV-1 is primarily found in CD4 ϩ T cells, while HTLV-2 is primarily found in CD8 ϩ T cells (21,43,46). In vitro, HTLV-1 preferentially transforms CD4 ϩ T cells while HTLV-2 preferentially transforms CD8 ϩ T cells, and this difference has been mapped to the Env proteins (54).…”

mentioning

confidence: 99%

The Receptor Complex Associated with Human T-Cell Lymphotropic Virus Type 3 (HTLV-3) Env-Mediated Binding and Entry Is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2

Jones

Huang

Chevalier

et al. 2009

J Virol

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Little is known about the transmission or tropism of the newly discovered human retrovirus, human T-cell lymphotropic virus type 3 (HTLV-3). Here, we examine the entry requirements of HTLV-3 using independently expressed Env proteins. We observed that HTLV-3 surface glycoprotein (SU) binds efficiently to both activated CD4 ؉ and CD8 ؉ T cells. This contrasts with both HTLV-1 SU, which primarily binds to activated CD4 ؉ T cells, and HTLV-2 SU, which primarily binds to activated CD8 ؉ T cells. Binding studies with heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), two molecules important for HTLV-1 entry, revealed that these molecules also enhance HTLV-3 SU binding. However, unlike HTLV-1 SU, HTLV-3 SU can bind efficiently in the absence of both HSPGs and NRP-1. Studies of entry performed with HTLV-3 Env-pseudotyped viruses together with SU binding studies revealed that, for HTLV-1, glucose transporter 1 (GLUT-1) functions at a postbinding step during HTLV-3 Env-mediated entry. Further studies revealed that HTLV-3 SU binds efficiently to naïve CD4 ؉ T cells, which do not bind either HTLV-1 or HTLV-2 SU and do not express detectable levels of HSPGs, NRP-1, and GLUT-1. These results indicate that the complex of receptor molecules used by HTLV-3 to bind to primary T lymphocytes differs from that of both HTLV-1 and HTLV-2.

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In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II).

Cited by 103 publications

References 25 publications

The Human T-cell leukemia virus Rex protein

The Human T-cell leukemia virus Rex protein

Induction of Human T Cell Leukemia Virus Type I Receptors on Quiescent Naive T Lymphocytes by TGF-β

The Receptor Complex Associated with Human T-Cell Lymphotropic Virus Type 3 (HTLV-3) Env-Mediated Binding and Entry Is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2

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