Molecular Biology of Friend Viral Erythroleukemia

Kabat, David

doi:10.1007/978-3-642-74700-7_1

Cited by 126 publications

(127 citation statements)

References 213 publications

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“…This rapid and vigorous expansion of erythroid progenitor cells accelerates the viral replication that leads to the highlevel viremia and provides a large pool of additional target cells for repeated integration of F-MuLVand SFFV proviruses. Ultimately, FVinfected mice develop erythroleukemia through promoter insertion or the silencing of a tumor suppressor gene (21) or, if able to recover from acute FV-induced disease, develop a life-long chronic infection (22).…”

mentioning

confidence: 99%

Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8+ T Cells by Rapid Induction of Multiple Inhibitory Receptors

Takamura¹,

Tsuji-Kawahara²,

Yagita

et al. 2010

The Journal of Immunology

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During chronic viral infection, persistent exposure to viral Ags leads to the overexpression of multiple inhibitory cell-surface receptors that cause CD8+ T cell exhaustion. The severity of exhaustion correlates directly with the level of infection and the number and intensity of inhibitory receptors expressed, and it correlates inversely with the ability to respond to the blockade of inhibitory pathways. Friend virus (FV) is a murine retrovirus complex that induces acute high-level viremia, followed by persistent infection and leukemia development, when inoculated into immunocompetent adult mice. In this article, we provide conclusive evidence that FV infection results in the generation of virus-specific effector CD8+ T cells that are terminally exhausted. Acute FV-induced disease is characterized by a rapid increase in the number of virus-infected erythroblasts, leading to massive splenomegaly. Most of the expanded erythroblasts strongly express programmed death ligand-1 and MHC class I, thereby creating a highly tolerogenic environment. Consequently, FV-specific effector CD8+ T cells uniformly express multiple inhibitory receptors, such as programmed cell death 1 (PD-1), T cell Ig domain and mucin domain 3 (Tim-3), lymphocyte activation gene-3, and CTLA-4, rapidly become nonresponsive to restimulation and are no longer reinvigorated by combined in vivo blockade of PD-1 and Tim-3 during the memory phase. However, combined blockade of PD-1 and Tim-3 during the priming/differentiation phase rescued FV-specific CD8+ T cells from becoming terminally exhausted, resulting in improved CD8+ T cell functionality and virus control. These results highlight FV’s unique ability to evade virus-specific CD8+ T cell responses and the importance of an early prophylactic approach for preventing terminal exhaustion of CD8+ T cells.

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confidence: 99%

Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8+ T Cells by Rapid Induction of Multiple Inhibitory Receptors

Takamura¹,

Tsuji-Kawahara²,

Yagita

et al. 2010

The Journal of Immunology

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“…Friend virus -induced erythroleukemias of mice have served as important model-for understanding the multistep aspects of leukemia development (2)(3)(4). The permanent murine erythroleukemia (MEL) cell lines that can be established from such mice (5,6) have also stimulated interest in approaches to cancer therapy based on forced differentiation of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming Leukemia Cells to Terminal Differentiation and Growth Arrest by RNA Interference of PU.1

Papetti

Skoultchi²

2007

Molecular Cancer Research

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Malignant transformation often leads to both loss of normal proliferation control and inhibition of cell differentiation. Some tumor cells can be stimulated to reenter their differentiation program and to undergo terminal growth arrest. The in vitro differentiation of mouse erythroleukemia (MEL) cells is an important example of tumor cell reprogramming. MEL cells are malignant erythroblasts that are blocked from differentiating into mature RBC due to dysregulated expression of the transcription factor PU

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“…Friend spleen focus-forming virus (F-SFFV) is a highly pathogenic, replication-defective retrovirus inducing acute erythroleukaemia in mice which is either associated with a polycythaemia (F-SFFVp) or a slight anaemia (for reviews, see Ruscetti & Wolff, 1984;Ostertag et al, 1987;Kabat, 1989). In both instances, the presence and expression of the viral envelope (env) gene was shown to be essential and sufficient for induction of the disease (Linemeyer et al, 1981(Linemeyer et al, , 1982Machida et al, 1985;Wolff & Ruscetti, 1985Li et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

“…Only a small proportion of the molecules is further processed in the Golgi apparatus yielding a glycoprotein with an Mr of about 65 000 (gp65) which carries complex-type carbohydrate chains (Srinivas & Compans, 1983;Strube & Geyer, 1989) as well as Olinked glycans (Pinter & Honnen, 1989;Gliniak & Kabat, 1989) and can be readily detected on the cell surface . It has been suggested that the surface expression of gp65 (Li et al, 1987) and, possibly, also shedding of the molecule from the plasma membrane by proteolytic cleavage of the membrane anchor from the C terminus (Pinter & Honnen, 1985, 1989Gliniak & Kabat, 1989) may be a prerequisite for the leukaemogenicity of F-SFFV F. Hence, intracellular transport and processing of the env gene product seem to be important for viral pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

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The role of gp55 N-glycosylation in pathogenesis of Friend spleen focus-forming virus

Rau

Geyer

Friedrich

1993

Journal of General Virology

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The product of the envelope gene (gp55) of Friend spleen focus-forming virus is responsible for the acute form of erythroleukaemia caused by this virus. In order to investigate the role that the four known N-linked carbohydrate side-chains of gp55 play in pathogenesis, we have inactivated the four N-glycosylation signals by mutating the asparagine residues of these four sites into serine. When glycosylation sites 1 and/or 2 were altered, the viruses remained fully pathogenic. However, mutation at either of glycosylation sites 3 or 4 rendered the virus apathogenic, independent of mutations at other sites. Furthermore, when site 3 was changed, a new product appeared which seemed to have acquired a carbohydrate chain at a position normally not glycosylated, presumably at position Asn~Ts.

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Molecular Biology of Friend Viral Erythroleukemia

Cited by 126 publications

References 213 publications

Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8+ T Cells by Rapid Induction of Multiple Inhibitory Receptors

Premature Terminal Exhaustion of Friend Virus-Specific Effector CD8+ T Cells by Rapid Induction of Multiple Inhibitory Receptors

Reprogramming Leukemia Cells to Terminal Differentiation and Growth Arrest by RNA Interference of PU.1

The role of gp55 N-glycosylation in pathogenesis of Friend spleen focus-forming virus

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