Targeting CCR5 trafficking to inhibit HIV-1 infection

被引：23

作者：

Boncompain, Gaelle ^{[1
]}

Herit, Floriane ^{[2
]}

Tessier, Sarah ^{[3
]}

Lescure, Aurianne ^{[3
]}

Del Nery, Elaine ^{[3
]}

Gestraud, Pierre ^{[4
]}

Staropoli, Isabelle ^{[5
]}

Fukata, Yuko ^{[6
]}

Fukata, Masaki ^{[6
]}

Brelot, Anne ^{[5
]}

Niedergang, Florence ^{[2
]}

Perez, Franck ^{[1
]}

机构：

[1] Sorbonne Univ, PSL Res Univ, Inst Curie, CNRS,UMR 144,Dynam Intracellular Org Lab, F-75005 Paris, France

[2] Univ Paris, Inst Cochin, INSERM, CNRS, F-75014 Paris, France

[3] PSL Res Univ, Inst Curie, Translat Dept, Biophen High Content Screening Lab, F-75005 Paris, France

[4] PSL Res Univ, Inst Curie, Bioinformat Facil, INSERM,U900, F-75005 Paris, France

[5] Inst Pasteur, INSERM, U1108, Viral Pathogenesis Unit,Dept Virol, F-75015 Paris, France

[6] Natl Inst Nat Sci, Natl Inst Physiol Sci, Dept Mol & Cellular Physiol, Div Membrane Physiol, Okazaki, Aichi 4448787, Japan

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 10期

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODY; T-CELLS; RECEPTOR; IDENTIFICATION; RESISTANCE; FUSION; MARAVIROC; PALMITOYLATION;

D O I：

10.1126/sciadv.aax0821

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Using a cell-based assay monitoring differential protein transport in the secretory pathway coupled to high-content screening, we have identified three molecules that specifically reduce the delivery of the major co-receptor for HIV-1, CCR5, to the plasma membrane. They have no effect on the closely related receptors CCR1 and CXCR4. These molecules are also potent in primary macrophages as they markedly decrease HIV entry. At the molecular level, two of these molecules inhibit the critical palmitoylation of CCR5 and thereby block CCR5 in the early secretory pathway. Our results open a clear therapeutics avenue based on trafficking control and demonstrate that preventing HIV infection can be performed at the level of its receptor delivery.

引用

页数：13

共 43 条

[31]

Nakashima T, 2000, CANCER RES, V60, P1229

[32] A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors [J].

Park, Ryan J. ;

Wang, Tim ;

Koundakjian, Dylan ;

Hultquist, Judd F. ;

Lamothe-Molina, Pedro ;

Monel, Blandine ;

Schumann, Kathrin ;

Yu, Haiyan ;

Krupzcak, Kevin M. ;

Garcia-Beltran, Wilfredo ;

Piechocka-Trocha, Alicja ;

Krogan, Nevan J. ;

Marson, Alexander ;

Sabatini, David M. ;

Lander, Eric S. ;

Hacohen, Nir ;

Walker, Bruce D. .

NATURE GENETICS, 2017, 49 (02) :193-203

[33] Palmitoylation-dependent control of degradation, life span, and membrane expression of the CCR5 receptor [J].

Percherancier, Y ;

Planchenault, T ;

Valenzuela-Fernandez, A ;

Virelizier, JL ;

Arenzana-Seisdedos, F ;

Bachelerie, F .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (34) :31936-31944

[34] Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases [J].

Perez, Elena E. ;

Wang, Jianbin ;

Miller, Jeffrey C. ;

Jouvenot, Yann ;

Kim, Kenneth A. ;

Liu, Olga ;

Wang, Nathaniel ;

Lee, Gary ;

Bartsevich, Victor V. ;

Lee, Ya-Li ;

Guschin, Dmitry Y. ;

Rupniewski, Igor ;

Waite, Adam J. ;

Carpenito, Carmine ;

Carroll, Richard G. ;

Orange, Jordan S. ;

Urnov, Fyodor D. ;

Rebar, Edward J. ;

Ando, Dale ;

Gregory, Philip D. ;

Riley, James L. ;

Holmes, Michael C. ;

June, Carl H. .

NATURE BIOTECHNOLOGY, 2008, 26 (07) :808-816

[35] Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry [J].

Pleskoff, O ;

Treboute, C ;

Brelot, A ;

Heveker, N ;

Seman, M ;

Alizon, M .

SCIENCE, 1997, 276 (5320) :1874-1878

[36] HIV-1 Escape from the CCR5 Antagonist Maraviroc Associated with an Altered and Less-Efficient Mechanism of gp120-CCR5 Engagement That Attenuates Macrophage Tropism [J].

Roche, Michael ;

Jakobsen, Martin R. ;

Sterjovski, Jasminka ;

Ellett, Anne ;

Posta, Filippo ;

Lee, Benhur ;

Jubb, Becky ;

Westby, Mike ;

Lewin, Sharon R. ;

Ramsland, Paul A. ;

Churchill, Melissa J. ;

Gorry, Paul R. .

JOURNAL OF VIROLOGY, 2011, 85 (09) :4330-4342

[37] Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene [J].

Samson, M ;

Libert, F ;

Doranz, BJ ;

Rucker, J ;

Liesnard, C ;

Farber, CM ;

Saragosti, S ;

Lapoumeroulie, C ;

Cognaux, J ;

Forceille, C ;

Muyldermans, G ;

Verhofstede, C ;

Burtonboy, G ;

Georges, M ;

Imai, T ;

Rana, S ;

Yi, YJ ;

Smyth, RJ ;

Collman, RG ;

Doms, RW ;

Vassart, G ;

Parmentier, M .

NATURE, 1996, 382 (6593) :722-725

[38] Cadmium-zinc exchange and their binary relationship in the structure of Zn-related proteins: a mini review [J].

Tang, Lu ;

Qiu, Rongliang ;

Tang, Yetao ;

Wang, Shizhong .

METALLOMICS, 2014, 6 (08) :1313-1323

[39] Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV [J].

Tebas, Pablo ;

Stein, David ;

Tang, Winson W. ;

Frank, Ian ;

Wang, Shelley Q. ;

Lee, Gary ;

Spratt, S. Kaye ;

Surosky, Richard T. ;

Giedlin, Martin A. ;

Nichol, Geoff ;

Holmes, Michael C. ;

Gregory, Philip D. ;

Ando, Dale G. ;

Kalos, Michael ;

Collman, Ronald G. ;

Binder-Scholl, Gwendolyn ;

Plesa, Gabriela ;

Hwang, Wei-Ting ;

Levine, Bruce L. ;

June, Carl H. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (10) :901-910

[40] A Maraviroc-Resistant HIV-1 with Narrow Cross-Resistance to Other CCR5 Antagonists Depends on both N-Terminal and Extracellular Loop Domains of Drug-Bound CCR5 [J].

Tilton, John C. ;

Wilen, Craig B. ;

Didigu, Chukwuka A. ;

Sinha, Rohini ;

Harrison, Jessamina E. ;

Agrawal-Gamse, Caroline ;

Henning, Elizabeth A. ;

Bushman, Frederick D. ;

Martin, Jeffrey N. ;

Deeks, Steven G. ;

Doms, Robert W. .

JOURNAL OF VIROLOGY, 2010, 84 (20) :10863-10876

← 1 2 3 4 5 →