2024年2月26日 / 最終更新日 : 2024年2月26日 ad_y ニュース

2024年 新着論文 16　細胞情報学分野から論文が発表されました

Host ZCCHC3 blocks HIV-1 infection and production through a dual mechanism

iScience. 2024 Feb 5;27(3):109107. doi: 10.1016/j.isci.2024.109107. eCollection 2024 Mar 15.

Authors

Binbin Yi  1 , Yuri L Tanaka  2 , Daphne Cornish  3   4 , Hidetaka Kosako  5 , Erika P Butlertanaka  2 , Prabuddha Sengupta  6 , Jennifer Lippincott-Schwartz  6 , Judd F Hultquist  3   4 , Akatsuki Saito  2   7   8 , Shige H Yoshimura  1   9

Affiliations

  • 1 Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.
  • 2 Department of Veterinary Medicine, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen Kibanadai-nishi, Miyazaki, Miyazaki 889-2192, Japan.
  • 3 Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • 4 Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA.
  • 5 Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
  • 6 Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
  • 7 Center for Animal Disease Control, University of Miyazaki, 1-1 Gakuen Kibanadai-nishi, Miyazaki, Miyazaki 889-2192, Japan.
  • 8 Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, 5200 Kiyotakecho Kihara, Miyazaki, Miyazaki 889-1692, Japan.
  • 9 Center for Living Systems Information Science (CeLiSIS), Kyoto University, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto 606-8501, Japan.

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.

Keywords: Biological sciences; Immunology; Virology.

Conflict of interest statement

J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences and is a paid consultant for Merck.
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