Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1

Michael Schindler; Jan Muench; Olaf Kutsch; Hui Li; Mario L. Santiago; Frederic Bibollet-Ruche; Michaela C. Muller-Trutwin; Francis J. Novembre; Martine Peeters; Valerie Courgnaud; Elizabeth Bailes; Pierre Roques; Donald L. Sodora; Guido Silvestri; Paul M. Sharp; Beatrice H. Hahn; Frank Kirchhoff

doi:10.1016/j.cell.2006.04.033

Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1

Michael Schindler, Jan Muench, Olaf Kutsch, Hui Li, Mario L. Santiago, Frederic Bibollet-Ruche, Michaela C. Muller-Trutwin, Francis J. Novembre, Martine Peeters, Valerie Courgnaud, Elizabeth Bailes, Pierre Roques, Donald L. Sodora, Guido Silvestri, Paul M. Sharp, Beatrice H. Hahn, Frank Kirchhoff

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses; that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.

Original language	English
Pages (from-to)	1055-1067
Number of pages	13
Journal	Cell
Volume	125
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2006.04.033
Publication status	Published - 16 Jun 2006

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Schindler, M., Muench, J., Kutsch, O., Li, H., Santiago, M. L., Bibollet-Ruche, F., Muller-Trutwin, M. C., Novembre, F. J., Peeters, M., Courgnaud, V., Bailes, E., Roques, P., Sodora, D. L., Silvestri, G., Sharp, P. M., Hahn, B. H., & Kirchhoff, F. (2006). Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell, 125(6), 1055-1067. https://doi.org/10.1016/j.cell.2006.04.033

@article{87eba08debd241739728249c109829a6,

title = "Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1",

abstract = "High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses; that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.",

author = "Michael Schindler and Jan Muench and Olaf Kutsch and Hui Li and Santiago, {Mario L.} and Frederic Bibollet-Ruche and Muller-Trutwin, {Michaela C.} and Novembre, {Francis J.} and Martine Peeters and Valerie Courgnaud and Elizabeth Bailes and Pierre Roques and Sodora, {Donald L.} and Guido Silvestri and Sharp, {Paul M.} and Hahn, {Beatrice H.} and Frank Kirchhoff",

year = "2006",

month = jun,

day = "16",

doi = "10.1016/j.cell.2006.04.033",

language = "English",

volume = "125",

pages = "1055--1067",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "6",

}

Schindler, M, Muench, J, Kutsch, O, Li, H, Santiago, ML, Bibollet-Ruche, F, Muller-Trutwin, MC, Novembre, FJ, Peeters, M, Courgnaud, V, Bailes, E, Roques, P, Sodora, DL, Silvestri, G, Sharp, PM, Hahn, BH & Kirchhoff, F 2006, 'Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1', Cell, vol. 125, no. 6, pp. 1055-1067. https://doi.org/10.1016/j.cell.2006.04.033

TY - JOUR

T1 - Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1

AU - Schindler, Michael

AU - Muench, Jan

AU - Kutsch, Olaf

AU - Li, Hui

AU - Santiago, Mario L.

AU - Bibollet-Ruche, Frederic

AU - Muller-Trutwin, Michaela C.

AU - Novembre, Francis J.

AU - Peeters, Martine

AU - Courgnaud, Valerie

AU - Bailes, Elizabeth

AU - Roques, Pierre

AU - Sodora, Donald L.

AU - Silvestri, Guido

AU - Sharp, Paul M.

AU - Hahn, Beatrice H.

AU - Kirchhoff, Frank

PY - 2006/6/16

Y1 - 2006/6/16

N2 - High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses; that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.

AB - High-level immune activation and T cell apoptosis represent a hallmark of HIV-1 infection that is absent from nonpathogenic SIV infections in natural primate hosts. The mechanisms causing these varying levels of immune activation are not understood. Here, we report that nef alleles from the great majority of primate lentiviruses, including HIV-2, downmodulate TCR-CD3 from infected T cells, thereby blocking their responsiveness to activation. In contrast, nef alleles from HIV-1 and a subset of closely related SIVs fail to downregulate TCR-CD3 and to inhibit cell death. Thus, Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses; that likely evolved to maintain viral persistence in the context of an intact host immune system. This function was lost during viral evolution in a lineage that gave rise to HIV-1 and may have predisposed the simian precursor of HIV-1 for greater pathogenicity in humans.

U2 - 10.1016/j.cell.2006.04.033

DO - 10.1016/j.cell.2006.04.033

M3 - Article

SN - 0092-8674

VL - 125

SP - 1055

EP - 1067

JO - Cell

JF - Cell

IS - 6

ER -

Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1

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