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

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bioRxiv. 2023 Jun 14;. doi: 10.1101/2023.06.14.544911

Host ZCCHC3 blocks HIV-1 infection and production by a dual mechanism Lippincott-Schwartz Lab

Yi Binbin, Tanaka Yuri, Kosako Hidetaka, Butlertanaka Erika, Sengupta Prabuddha, Lippincott-Schwartz Jennifer, Saito Akatsuki, Yoshimura Shige

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Abstract

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.

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bioRxiv PrePrint https://doi.org/10.1101/2023.06.14.544911

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

Abstract

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