دورية أكاديمية
Nef defect attenuates HIV viremia and immune dysregulation in the bone marrow-liver-thymus-spleen (BLTS) humanized mouse model.
| العنوان: | Nef defect attenuates HIV viremia and immune dysregulation in the bone marrow-liver-thymus-spleen (BLTS) humanized mouse model. |
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| المؤلفون: | Biradar S; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Agarwal Y; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Das A; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Shu ST; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Samal J; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Ho S; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Kelly N; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Mahesh D; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Teredesai S; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Castronova I; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Mussina L; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Mailliard RB; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA., Smithgall TE; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Bility MT; Department of Infectious Diseases and Microbiology, University of Pittsburgh, School of Public Health, Pittsburgh, PA, USA; Department of Microbiology, Howard University, Washington, DC, USA. Electronic address: moses.bility@howard.edu. |
| المصدر: | Virology [Virology] 2024 Oct; Vol. 598, pp. 110192. Date of Electronic Publication: 2024 Jul 31. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0110674 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0341 (Electronic) Linking ISSN: 00426822 NLM ISO Abbreviation: Virology Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, Academic Press. |
| مواضيع طبية MeSH: | nef Gene Products, Human Immunodeficiency Virus*/genetics , nef Gene Products, Human Immunodeficiency Virus*/immunology , HIV Infections*/immunology , HIV Infections*/virology , Viremia*/immunology , Spleen*/immunology , Spleen*/virology , Disease Models, Animal* , HIV-1*/immunology , HIV-1*/genetics , HIV-1*/physiology , Liver*/virology , Liver*/immunology , Liver*/pathology , Virus Replication*, Animals ; Mice ; Humans ; Bone Marrow/virology ; Bone Marrow/immunology ; Thymus Gland/immunology ; Thymus Gland/virology ; Immunity, Innate |
| مستخلص: | In vitro studies have shown that deletion of nef and deleterious mutation in the Nef dimerization interface attenuates HIV replication and associated pathogenesis. Humanized rodents with human immune cells and lymphoid tissues are robust in vivo models for investigating the interactions between HIV and the human immune system. Here, we demonstrate that nef deletion impairs HIV replication and HIV-induced immune dysregulation in the blood and human secondary lymphoid tissue (human spleen) in bone marrow-liver-thymus-spleen (BLTS) humanized mice. Furthermore, we also show that nef defects (via deleterious mutations in the dimerization interface) impair HIV replication and HIV-induced immune dysregulation in the blood and human spleen in BLTS-humanized mice. We demonstrate that the reduced replication of nef-deleted and nef-defective HIV is associated with robust antiviral innate immune response, and T helper 1 response. Our results support the proposition that Nef may be a therapeutic target for adjuvants in HIV cure strategies. Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | R01 AI152655 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: BLTS-Humanized mice; HIV nef; Immune dysregulation |
| المشرفين على المادة: | 0 (nef Gene Products, Human Immunodeficiency Virus) 0 (nef protein, Human immunodeficiency virus 1) |
| تواريخ الأحداث: | Date Created: 20240806 Date Completed: 20240812 Latest Revision: 20240812 |
| رمز التحديث: | 20240813 |
| DOI: | 10.1016/j.virol.2024.110192 |
| PMID: | 39106585 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1096-0341 |
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| DOI: | 10.1016/j.virol.2024.110192 |