Periprosthetic joint infections.

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Abstract

3. J Biol Chem. 2024 Sep;300(9):107701. doi: 10.1016/j.jbc.2024.107701. Epub 2024 Aug 22. A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24. Nyame P(1), Togami A(2), Yoshida T(1), Masunaga T(2), Begum MM(3), Terasawa H(1), Monde N(1), Tahara Y(2), Tanaka R(4), Tanaka Y(4), Appiah-Kubi J(1), Amesimeku WAO(1), Hossain MJ(1), Otsuka M(5), Yoshimura K(6), Ikeda T(3), Sawa T(1), Satou Y(7), Fujita M(2), Maeda Y(8), Tateishi H(9), Monde K(10). Author information: (1)Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. (2)Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. (3)Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan. (4)Laboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Okinawa, Japan. (5)Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Department of Drug Discovery, Science Farm Ltd, Kumamoto, Japan. (6)Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan. (7)Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan. (8)Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Department of Nursing, Kibi International University, Takahashi, Japan. (9)Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Research & Development, Hirata Corporation, Kumamoto, Japan. Electronic address: htateishi@kumamoto-u.ac.jp. (10)Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan. Electronic address: monde@kumamoto-u.ac.jp. The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.jbc.2024.107701 PMCID: PMC11419809