title: Chimeric Trojan Protein Insertion in Lentiviral Membranes Makes Lentiviruses Susceptible to Neutralization by Anti-Tetanus Serum Antibodies.
abstract: This study describes the initial testing of a novel strategy for neutralization of lentiviruses using the fundamental biology of enveloped viruses' assembly and budding. In the field of gene therapy, viral vector surface proteins have been manipulated in order to redirect host cell specificity by alteration of pseudo-types. This study tested whether known viral pseudo-typing proteins or surface proteins known to be recruited to the human immunodeficiency virus (HIV) envelope could be engineered to carry neutralizing epitopes from another microorganism onto the lentiviral surface. The results identify ICAM1 as a novel vehicle for lentiviral pseudo-typing. Importantly, the study shows that in a model lentiviral system, ICAM1 can be engineered in chimeric form to result in expression of a fragment of the tetanus toxoid on the viral membrane and that these viruses can then be neutralized by human serum antibodies protective against tetanus. This raises the possibility of delivering chimeric antigens as a gene therapy in HIV-infected patients.
authors.affiliation: 1 Centre of Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London , Egham, United Kingdom .
authors.forename: Anita
authors.initials: A
authors.lastname: Le Heron
authors.affiliation: 2 Department of Immunology, Imperial College London , London, United Kingdom .
authors.forename: Steven
authors.initials: S
authors.lastname: Patterson
authors.affiliation: 1 Centre of Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London , Egham, United Kingdom .
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Yáñez-Muñoz
authors.affiliation: 1 Centre of Biomedical Sciences, School of Biological Sciences, Royal Holloway University of London , Egham, United Kingdom .
authors.forename: George
authors.initials: G
authors.lastname: Dickson
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D002462:Cell Membrane / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016086:Lentivirus / Q000276:immunology*; D009500:Neutralization Tests; D013742:Tetanus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015699:HIV Envelope Protein gp120; C573420:ICAM1 protein, human; D018799:Intercellular Adhesion Molecule-1
keywords: HIV; chimeric protein; lentiviral; neutralization; tetanus