HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

Christine Goffinet; Ina Allespach; Stefanie Homann; Hanna Mari Tervo; Anja Habermann; Daniel Rupp; Lena Oberbremer; Christian Kern; Nadine Tibroni; Sonja Welsch; Jacomine Krijnse-Locker; George Banting; Hans Georg Kräusslich; Oliver T. Fackler; Oliver T. Keppler

doi:10.1016/j.chom.2009.01.009

HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

Christine Goffinet, Ina Allespach, Stefanie Homann, Hanna Mari Tervo, Anja Habermann, Daniel Rupp, Lena Oberbremer, Christian Kern, Nadine Tibroni, Sonja Welsch, Jacomine Krijnse-Locker, George Banting, Hans Georg Kräusslich, Oliver T. Fackler, Oliver T. Keppler

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

235 Citations (Scopus)

Abstract

Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.

Original language	English
Pages (from-to)	285-297
Number of pages	13
Journal	Cell Host and Microbe
Volume	5
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2009.01.009
Publication status	Published - 19 Mar 2009
Externally published	Yes

Keywords

MICROBIO
MOLIMMUNO

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2009.01.009

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Goffinet, C., Allespach, I., Homann, S., Tervo, H. M., Habermann, A., Rupp, D., Oberbremer, L., Kern, C., Tibroni, N., Welsch, S., Krijnse-Locker, J., Banting, G., Kräusslich, H. G., Fackler, O. T., & Keppler, O. T. (2009). HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor. Cell Host and Microbe, 5(3), 285-297. https://doi.org/10.1016/j.chom.2009.01.009

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title = "HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor",

abstract = "Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.",

keywords = "MICROBIO, MOLIMMUNO",

author = "Christine Goffinet and Ina Allespach and Stefanie Homann and Tervo, \{Hanna Mari\} and Anja Habermann and Daniel Rupp and Lena Oberbremer and Christian Kern and Nadine Tibroni and Sonja Welsch and Jacomine Krijnse-Locker and George Banting and Kr{\"a}usslich, \{Hans Georg\} and Fackler, \{Oliver T.\} and Keppler, \{Oliver T.\}",

year = "2009",

month = mar,

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doi = "10.1016/j.chom.2009.01.009",

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Goffinet, C, Allespach, I, Homann, S, Tervo, HM, Habermann, A, Rupp, D, Oberbremer, L, Kern, C, Tibroni, N, Welsch, S, Krijnse-Locker, J, Banting, G, Kräusslich, HG, Fackler, OT & Keppler, OT 2009, 'HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor', Cell Host and Microbe, vol. 5, no. 3, pp. 285-297. https://doi.org/10.1016/j.chom.2009.01.009

TY - JOUR

T1 - HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

AU - Goffinet, Christine

AU - Allespach, Ina

AU - Homann, Stefanie

AU - Tervo, Hanna Mari

AU - Habermann, Anja

AU - Rupp, Daniel

AU - Oberbremer, Lena

AU - Kern, Christian

AU - Tibroni, Nadine

AU - Welsch, Sonja

AU - Krijnse-Locker, Jacomine

AU - Banting, George

AU - Kräusslich, Hans Georg

AU - Fackler, Oliver T.

AU - Keppler, Oliver T.

PY - 2009/3/19

Y1 - 2009/3/19

N2 - Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.

AB - Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major structural domains of CD317. To promote virus release, Vpu depletes cellular pools of human CD317, but not of the rodent orthologs, by accelerating its degradation via the 20S proteasome. Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection.

KW - MICROBIO

KW - MOLIMMUNO

U2 - 10.1016/j.chom.2009.01.009

DO - 10.1016/j.chom.2009.01.009

M3 - Article

SN - 1931-3128

VL - 5

SP - 285

EP - 297

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

Abstract

Keywords

UN SDGs

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