title: CCR5 as a natural and modulated target for inhibition of HIV.
abstract: 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.
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. bryan.burke@calimmuneinc.com.
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Burke
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. maureen.boyd@calimmuneinc.com.
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Boyd
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. helen.impey@calimmuneinc.com.
authors.forename: Helen
authors.initials: H
authors.lastname: Impey
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. louis.breton@calimmuneinc.com.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Breton
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. jeffrey.bartlett@calimmuneinc.com.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Bartlett
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. geoff.symonds@calimmuneinc.com.
authors.forename: Geoff P
authors.initials: GP
authors.lastname: Symonds
authors.affiliation: Calimmune, Inc., Los Angeles, California, CA 90024, USA. gero.huetter@medma.uni-heidelberg.de.
authors.forename: Gero
authors.initials: G
authors.lastname: Hütter
mesh_terms: D001691:Biological Therapy / Q000379:methods; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology / Q000821:virology; D006801:Humans; D019713:Receptors, CCR5 / Q000096:biosynthesis; D015728:Receptors, HIV / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C515020:C46 HIV-1 fusion inhibitory peptide; D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; D019713:Receptors, CCR5; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins