title: A monoclonal antibody directed against a conformational epitope of the HIV-1 trans-activator (Tat) protein neutralizes cross-clade.
abstract: The identification of a neutralizing mAb against extracellular HIV-1 transactivator of transcription (Tat) is important for the development of an efficient HIV-1 treatment. Tat plays an essential role in HIV-1 pathogenesis, not only for HIV-1 replication but also as an extracellular toxin able to disrupt the immune system. We showed previously that immunization of rabbits with Tat Oyi, a variant cloned from an African woman who did not develop AIDS following HIV-1 infection, raised antibodies able to recognize different Tat variants. We carried out mice immunization with Tat Oyi and selected a mAb named 7G12, which had the capacity to cross-recognize heterologous Tat variants by a common three-dimensional epitope. These results highlighted that Tat variants were able to acquire a structure, in contrast to a number of studies showing Tat as an unfolded protein. mAb 7G12 also had the capacity to neutralize the biological activities of these Tat variants by blocking the cellular uptake of extracellular Tat. This is the first study using Tat Oyi to produce a mAb able to neutralize effectively activities of extracellular Tats from different HIV-1 subtypes. This mAb has an important potential in therapeutic passive immunization and could help HIV-1 infected patients to restore their immunity.
authors.affiliation: Equipe de Recherche Technologique 2011, Université de la Méditerranée, Faculté de Pharmacie, 27 BD Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mediouni
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Watkins
authors.forename: Michel
authors.initials: M
authors.lastname: Pierres
authors.forename: Angélique
authors.initials: A
authors.lastname: Bole
authors.forename: Erwann P
authors.initials: EP
authors.lastname: Loret
authors.forename: Gilbert
authors.initials: G
authors.lastname: Baillat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry* / Q000494:pharmacology; D000915:Antibody Affinity; D000918:Antibody Specificity; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000939:Epitopes; D054322:tat Gene Products, Human Immunodeficiency Virus