@article {68831,
	title = {Host ZCCHC3 blocks HIV-1 infection and production by a dual mechanism},
	journal = {iScience},
	year = {2024},
	month = {05/2024},
	abstract = {<p>Most mammalian cells prevent viral infection and proliferation by expressing various restriction factors and sensors that activate the immune system. While anti-human immunodeficiency virus type 1 (HIV-1) host restriction factors have been identified, most of them are antagonized by viral proteins. This has severely hindered their development in anti-HIV-1 therapy. Here, we describe CCHC-type zinc-finger-containing protein 3 (ZCCHC3) as a novel anti-HIV-1 factor that is not antagonized by viral proteins. ZCCHC3 suppresses production of HIV-1 and other retroviruses. We show that ZCCHC3 acts by binding to Gag nucleocapsid protein via zinc-finger motifs. This prevents interaction between the Gag nucleocapsid protein and viral genome and results in production of genome-deficient virions. 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. Such a dual antiviral mechanism is distinct from that of any other known host restriction factors. Therefore, ZCCHC3 is a novel potential target in anti-HIV-1 therapy.</p>
},
	doi = {10.1101/2023.06.14.544911},
	url = {https://doi.org/10.1101/2023.06.14.544911},
	author = {Binbin Yi and Yuri L Tanaka and Hidetaka Kosako and Erika P Butlertanaka and Prabuddha Sengupta and Jennifer Lippincott-Schwartz and Akatsuki Saito and Shige H. Yoshimura}
}
