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Envelope protein-specific B cell receptors direct lentiviral vector tropism in vivo.
Takano, Kari-Ann; Wong, Anita A L; Brown, Rebecca; Situ, Kathy; Chua, Bernadette Anne; Abu, Angel Elma; Pham, Truc T; Reyes, Glania Carel; Ramachandran, Sangeetha; Kamata, Masakazu; Li, Melody M H; Wu, Ting-Ting; Rao, Dinesh S; Arumugaswami, Vaithilingaraja; Dorshkind, Kenneth; Cole, Steve; Morizono, Kouki.
Afiliación
  • Takano KA; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wong AAL; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Brown R; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Situ K; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Chua BA; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Abu AE; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Pham TT; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Reyes GC; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ramachandran S; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kamata M; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
  • Li MMH; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medi
  • Wu TT; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center
  • Rao DS; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medici
  • Arumugaswami V; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, Unive
  • Dorshkind K; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Cole S; Departments of Psychiatry & Biobehavioral Sciences and Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Morizono K; Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address
Mol Ther ; 32(5): 1311-1327, 2024 May 01.
Article en En | MEDLINE | ID: mdl-38449314
ABSTRACT
While studying transgene expression after systemic administration of lentiviral vectors, we found that splenic B cells are robustly transduced, regardless of the types of pseudotyped envelope proteins. However, the administration of two different pseudotypes resulted in transduction of two distinct B cell populations, suggesting that each pseudotype uses unique and specific receptors for its attachment and entry into splenic B cells. Single-cell RNA sequencing analysis of the transduced cells demonstrated that different pseudotypes transduce distinct B cell subpopulations characterized by specific B cell receptor (BCR) genotypes. Functional analysis of the BCRs of the transduced cells demonstrated that BCRs specific to the pseudotyping envelope proteins mediate viral entry, enabling the vectors to selectively transduce the B cell populations that are capable of producing antibodies specific to their envelope proteins. Lentiviral vector entry via the BCR activated the transduced B cells and induced proliferation and differentiation into mature effectors, such as memory B and plasma cells. BCR-mediated viral entry into clonally specific B cell subpopulations raises new concepts for understanding the biodistribution of transgene expression after systemic administration of lentiviral vectors and offers new opportunities for BCR-targeted gene delivery by pseudotyped lentiviral vectors.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transducción Genética / Linfocitos B / Receptores de Antígenos de Linfocitos B / Proteínas del Envoltorio Viral / Lentivirus / Transgenes / Vectores Genéticos Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Transducción Genética / Linfocitos B / Receptores de Antígenos de Linfocitos B / Proteínas del Envoltorio Viral / Lentivirus / Transgenes / Vectores Genéticos Límite: Animals / Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos