CCR5 as a Natural and Modulated Target for Inhibition of HIV

被引：27

作者：

Burke, Bryan P. ^{[1
]}

Boyd, Maureen P. ^{[1
]}

Impey, Helen ^{[1
]}

Breton, Louis R. ^{[1
]}

Bartlett, Jeffrey S. ^{[1
]}

Symonds, Geoff P. ^{[1
]}

Huetter, Gero ^{[2
,3
]}

机构：

[1] Calimmune Inc, Los Angeles, CA 90024 USA

[2] Heidelberg Univ, German Red Cross Blood Serv Baden Wurttemberg Hes, Med Fac Mannheim, Inst Transfus Med & Immunol, D-68167 Mannheim, Germany

[3] Cellex GmbH, D-01307 Dresden, Germany

来源：

VIRUSES-BASEL | 2014年 / 6卷 / 01期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

CCR5; C46; gene therapy; HIV; stem cell transplantation; SHORT HAIRPIN RNA; CD4(+) T-CELLS; GENE-THERAPY; IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR-5; INFECTED PATIENTS; ADOPTIVE TRANSFER; LYMPHOCYTES; EXPRESSION; POLYMORPHISM;

D O I：

10.3390/v6010054

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a patient with HIV ("Berlin patient") achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5-and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells.

引用

页码：54 / 68

页数：15

共 57 条

[1] Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation [J].

Allers, Kristina ;

Huetter, Gero ;

Hofmann, Joerg ;

Loddenkemper, Christoph ;

Rieger, Kathrin ;

Thiel, Eckhard ;

Schneider, Thomas .

BLOOD, 2011, 117 (10) :2791-2799

[2] Anti-human immunodeficiency virus hematopoietic progenitor cell-delivered ribozyme in a phase I study: Myeloid and lymphoid reconstitution in human immunodeficiency virus type-1-infected patients [J].

Amado, RG ;

Mitsuyasu, RT ;

Rosenblatt, JD ;

Ngok, FK ;

Bakker, A ;

Cole, S ;

Chorn, N ;

Lin, LS ;

Bristol, G ;

Boyd, MP ;

Macpherson, JL ;

Fanning, GC ;

Todd, AV ;

Ely, JA ;

Zack, JA ;

Symonds, GP .

HUMAN GENE THERAPY, 2004, 15 (03) :251-262

[3] Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates [J].

An, Dong Sung ;

Donahue, Robert E. ;

Karnata, Masakazu ;

Poon, Betty ;

Metzger, Mark ;

Mao, Si-Hua ;

Bonifacino, Aylin ;

Krouse, Allen E. ;

Darlix, Jean-Luc ;

Baltimore, David ;

Qin, F. Xiao-Feng ;

Chen, Irvin S. Y. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (32) :13110-13115

[4] Optimization and functional effects of stable short hairpin RNA expression in primary human lymphocytes via lentiviral vectors [J].

An, Dong Sung ;

Qin, F. Xiao-Feng ;

Auyeung, Vincent C. ;

Mao, Si Hua ;

Kung, Sam K. P. ;

Baltimore, David ;

Chen, Irvin S. Y. .

MOLECULAR THERAPY, 2006, 14 (04) :494-504

[5] CC chemokine receptor 5 polymorphism in Italian patients with Behcet's disease [J].

Atzeni, Fabiola ;

Boiardi, Luigi ;

Casali, Bruno ;

Farnetti, Enrico ;

Nicoli, Davide ;

Sarzi-Puttini, Piercarlo ;

Pipitone, Nicolo ;

Olivieri, Ignazio ;

Cantini, Fabrizio ;

Salvi, Fabrizio ;

La Corte, Renato ;

Triolo, Giovanni ;

Filippini, Davide ;

Paolazzi, Giuseppe ;

Salvarani, Carlo .

RHEUMATOLOGY, 2012, 51 (12) :2141-2145

[6]

Bogunia-Kubik K, 2006, HAEMATOLOGICA, V91, P1628

[7] A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy [J].

Deeks, SG ;

Wagner, B ;

Anton, PA ;

Mitsuyasu, RT ;

Scadden, DT ;

Haung, C ;

Macken, C ;

Richman, DD ;

Christopherson, C ;

June, CH ;

Lazar, R ;

Broad, DF ;

Jalali, S ;

Hege, KM .

MOLECULAR THERAPY, 2002, 5 (06) :788-797

[8]

Diez-Martin J.L., 2012, COMMUNICATION

[9] Gene therapy clinical trials worldwide to 2007 - an update [J].

Edelstein, Michael L. ;

Abedi, Mohammad R. ;

Wixon, Jo .

JOURNAL OF GENE MEDICINE, 2007, 9 (10) :833-842

[10] Inhibition of human immunodeficiency virus type 1 entry in cells expressing gp41-derived peptides [J].

Egelhofer, M ;

Brandenburg, G ;

Martinius, H ;

Schult-Dietrich, P ;

Melikyan, G ;

Kunert, R ;

Baum, C ;

Choi, I ;

Alexandrov, A ;

von Laer, D .

JOURNAL OF VIROLOGY, 2004, 78 (02) :568-575

← 1 2 3 4 5 6 →