Host ZCCHC3 blocks HIV-1 infection and production through a dual mechanism
Year: 2024
Type: article
Abstract: Most mammalian cells prevent viral infection and proliferation by expressing various restriction factors and sensors that activate the immune system. Several host restriction factors that inhibit human immunodeficiency virus type 1 (HIV-1) have been identified, but most of them are antagonized by viral proteins. Here, we describe CCHC-type zinc-finger-containing protein 3 (ZCCHC3) as a novel HIV-1 restriction factor that suppresses the production of HIV-1 and other retroviruses, but does not appear to be directly antagonized by viral proteins. It acts by binding to Gag nucleocapsid (GagNC) via zinc-finger motifs, which inhibits viral genome recruitment and results in genome-deficient virion production. ZCCHC3 also binds to the long terminal repeat on the viral genome via the middle-folded domain, sequestering the viral genome to P-bodies, which leads to decreased viral replication and production. This distinct, dual-acting antiviral mechanism makes upregulation of ZCCHC3 a novel potential therapeutic strategy.
Source: iScience
Institutions: Kyoto University, University of Miyazaki, Northwestern University, Institute of Advanced Medical Sciences, Tokushima University, Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima University, Howard Hughes Medical Institute, Janelia Research Campus, Center for Living Systems Information Science, Kyoto University
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: Houston Advanced Research Center, Japan Agency for Medical Research and Development, Third Coast Center for AIDS Research, University of Tokyo, University of Tokushima, National Institutes of Health, Center for AIDS Research, University of Washington, Japan Society for the Promotion of Science, Institute of Medical Science, University of Tokyo, Research Institute for Microbial Diseases, Osaka University, National Institute of Allergy and Infectious Diseases, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
Awards: Promotion of comprehensive interdisciplinary virology for the post-COVID era, G1350352333, G191015451, Donor-specific anti-HIV/SIV immunity mediated by APOBEC3 enzymes, HIV感染霊長類モデルを用いたHIV根治療法の有効性評価に関する研究, G2612887765, Molecular characterization of innate immune responses during HIV-1 and Zika virus coinfection of macrophages, Structural and functional regulation of intracellular membrane-less organelles by post-translational modifications., Regulation of SAMHD1 antiviral activity, G4839019089, Functionally Defining HIV-Host Interactions During the Early HIV-1 Lifecycle, G534236435, Exploring Small Molecule Inhibitors of PAF1C as Novel HIV Latency Reversal Agents, 留守家庭児童の特質に関する教育心理学的研究, G5541305092, 高親和性ACE2による逃避変異を克服するCOVID-19治療薬の開発, G5813651175, G619466266, ウイルス蛋白質の非構造領域による液相制御の解明と治療への応用, Elucidation of molecular determinants for species specificity of flaviviruses, Turning off HIV White Noise: Switching from Long-Lived to Short-Lived Reservoir, Deciphering the Role of CPSF6 in HIV Infection, Third Coast Center for AIDS Research, HARC: HIV accessory and regulatory complexes, Controlling HIV latency by manipulating CycT1 turnover
OpenAlex ID: W4391538579