CD4 down modulation on T-cells: an 'immune' checkpoint for HIV

Marodon, Gilles

doi:10.1016/s0165-2478(01)00286-3

Cited by 7 publications

(4 citation statements)

References 21 publications

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“…HRES-1/Rab4 promoter activities and protein levels are increased in cells infected by HIV-1 or transfected by HIV-tat. In turn, enhanced expression of HRES-1/Rab4 may contribute to down-regulation of CD4 recycling to the cell surface, thus preventing reinfection by HIV-1, allowing for increased virion production, and protecting virus-infected cells against killing by cytotoxic T cells (53,54). Thus, stimulation of HRES-1/Rab4 expression by HIV-1 and regulation of HIV coreceptor CD4 recycling by HRES-1/Rab4 represent novel mechanisms of coordinate interaction between infectious viral particles and ERV of the human genome.…”

Section: Discussionmentioning

confidence: 99%

Regulation of CD4 Expression via Recycling by HRES-1/RAB4 Controls Susceptibility to HIV Infection

Nagy

Ward

Mosser

et al. 2006

Journal of Biological Chemistry

112

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Section: Discussionmentioning

confidence: 99%

Regulation of CD4 Expression via Recycling by HRES-1/RAB4 Controls Susceptibility to HIV Infection

Nagy

Ward

Mosser

et al. 2006

Journal of Biological Chemistry

112

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“…Our results hinted that IDO may impair T cell-mediated immune responses by downregulation of the cell surface CD4 expression. Although CD4 downregulation can be carried out by HIV-1 virus protein, such as HIV-1 Nef [37,38], it is interesting to discuss why cellular proteins, such as IDO, downregulate the cell surface CD4 molecule. Our results indicated that IDO induced downregulation of CD4 in MT-2 and C8166 cells.…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule

Huang

Zeng

Liang

et al. 2012

IJMS

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Indoleamine 2,3-dioxygenase (IDO) has been implicated in preventing the fetus from undergoing maternal T cell-mediated immune responses, yet the mechanism underlying these kinds of IDO-mediated immune responses has not been fully elucidated. Since the CD4 molecule plays a central role in the onset and regulation of antigen-specific immune responses, and T cell is sensitive in the absence of tryptophan, we hypothesize that IDO may reduce cell surface CD4 expression. To test this hypothesis, an adenoviral vector-based construct IDO-EGFP was generated and the effect of IDO-EGFP on CD4 expression was determined on recombinant adenoviral infected C8166 and MT-2 cells, by flow cytometry and/or Western blot analysis. The results revealed a significant downregulation of cell membrane CD4 in pAd-IDOEGFP infected cells when compared to that of mock-infected cells or infection with empty vector pAd-EGFP. Further experiments disclosed that either an addition of tryptophan or IDO inhibitor could partly restore CD4 expression in pAd-IDOEGFP infected C8166 cells. Our findings suggest that downregulation of CD4 by IDO might be one of the mechanisms through which IDO regulates T cell-mediated immune responses.

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“…This is not unexpected, since Nef exploits a central transport pathway of eukaryotic cells by triggering CD4 endocytosis via clathrin-coated vesicles and subsequent lysosomal degradation (24). The efficient downregulation of CD4 appears to be of great importance for HIV, since Env and Vpu also exert this function (41). The loss of cell surface CD4 is believed to prevent viral superinfection and to counteract negative effects of CD4 on particle release and virion infectivity (6,35,51).…”

Section: Discussionmentioning

confidence: 99%

Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef

Keppler

Allespach

Schüller

et al. 2005

J Virol

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After infection with human immunodeficiency virus (HIV), progression toward immunodeficiency is governed by a complex interplay of viral and host determinants. The viral accessory protein Nef is a key factor for the development of AIDS. Strains of HIV and simian immunodeficiency virus that lack functional nef genes either do not induce AIDS or do so only after a significant delay. The validity of a transgenic-small-animal model for de novo infection by HIV will depend on its ability to recapitulate the actions of critical factors of viral pathogenicity, such as Nef. We assessed the ability of rat, mouse, and hamster cells to support key effector functions of Nef. In cell lines from rodents, the subcellular distribution of wild-type HIV type 1 strain SF2 Nef and mutants was comparable to that in human cells. Nef downregulated human CD4 from the cell surface, was associated with p21-activated kinase activity, and enhanced the infectivity of HIV-1 virions. Importantly, these Nef-induced effects, as well as the downregulation of rat CD4 and major histocompatibility complex class I molecules, could also be demonstrated in primary T lymphocytes and macrophages from human CD4-transgenic rats. Thus, HIV-1 Nef exerts key functions in rodent cells. In line with our ongoing efforts to establish a transgenic-rat model of HIV disease, these results indicate that important aspects of viral pathogenesis could be addressed in a transgenic-rodent model permissive for de novo infection and that such a model would be valuable for evaluating the function of Nef in vivo.

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CD4 down modulation on T-cells: an 'immune' checkpoint for HIV

Cited by 7 publications

References 21 publications

Regulation of CD4 Expression via Recycling by HRES-1/RAB4 Controls Susceptibility to HIV Infection

Regulation of CD4 Expression via Recycling by HRES-1/RAB4 Controls Susceptibility to HIV Infection

Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule

Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef

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