Proteomic analysis reveals zinc-finger CCHC-type containing protein 3 as a factor inhibiting virus infection by promoting innate signaling

Wang, Shuaiwei; Tong, Guangzhi; Chen, Keyuan; Zhao, Yan

doi:10.1016/j.virusres.2022.198876

Cited by 7 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 49 Previously, ZCCHC3 ZnF was shown to bind to dsRNA and poly I:C with a K d of 40 nM, although the protein fragment assayed in the previous study (aa 300–404) also contained a part of the MF domain. 24 Mutagenesis experiments presented herein revealed that two basic residues of ZCCHC3, R168 and R247, are involved in viral RNA binding ( Figure 5 F). These two residues are predicted to be located opposite one another within the middle cleft ( Figure 5 A).…”

Section: Discussionmentioning

confidence: 73%

“…ZCCHC3 has been shown to function with cGAS, 21 RIG-I, 22 and TLR3, 23 major cytoplasmic nucleic acid sensors that activate the innate immune signaling pathway, to regulate interferon-stimulated gene (ISG) expression, resulting in the degradation of viral RNA. 24 ZCCHC3 acts together with cGAS to recognize double-stranded (ds)DNA and with RIG-I and TLR3 to recognize dsRNA, although no direct physical interaction between ZCCHC3 and these proteins has been reported. Porcine ZCCHC3 has also been shown to suppress the replication of the pseudorabies virus by activating IFN-β expression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Yi,

Tanaka,

Cornish

et al. 2024

iScience

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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

Yi,

Tanaka,

Cornish

et al. 2024

iScience

View full text Add to dashboard Cite

“…In the same year, Taylor et al [ 22 ] reported inhibitory effects of ZCCHC3 on L1 activity in a cell culture assay for retrotransposition. Since then, ZCCHC3 has been shown to be part of the SARS-CoV-2 virus protein interactome [ 23 , 24 ] and to inhibit avian H9N2 virus and pseudorabies virus through type I IFN signaling [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

ZCCHC3 is a stress granule zinc knuckle protein that strongly suppresses LINE-1 retrotransposition

Goodier,

Wan,

Soares

et al. 2023

PLoS Genet

View full text Add to dashboard Cite

Retrotransposons have generated about half of the human genome and LINE-1s (L1s) are the only autonomously active retrotransposons. The cell has evolved an arsenal of defense mechanisms to protect against retrotransposition with factors we are only beginning to understand. In this study, we investigate Zinc Finger CCHC-Type Containing 3 (ZCCHC3), a gag-like zinc knuckle protein recently reported to function in the innate immune response to infecting viruses. We show that ZCCHC3 also severely restricts human retrotransposons and associates with the L1 ORF1p ribonucleoprotein particle. We identify ZCCHC3 as a bona fide stress granule protein, and its association with LINE-1 is further supported by colocalization with L1 ORF1 protein in stress granules, dense cytoplasmic aggregations of proteins and RNAs that contain stalled translation pre-initiation complexes and form when the cell is under stress. Our work also draws links between ZCCHC3 and the anti-viral and retrotransposon restriction factors Mov10 RISC Complex RNA Helicase (MOV10) and Zinc Finger CCCH-Type, Antiviral 1 (ZC3HAV1, also called ZAP). Furthermore, collective evidence from subcellular localization, co-immunoprecipitation, and velocity gradient centrifugation connects ZCCHC3 with the RNA exosome, a multi-subunit ribonuclease complex capable of degrading various species of RNA molecules and that has previously been linked with retrotransposon control.

show abstract

“…CCHC-type zinc-finger-containing protein 3 (ZCCHC3; [NP_149080.2]) is a host factor with a potential antiviral activity. It was initially identified by an interactome analysis on the basis of its interaction with HIV-1 Gag 26 and was eventually shown to regulate the activity of the interferonstimulated response gene (ISG), which reduced the virus replication by degrading viral RNA 27 . It functionally interacts with cGAS 28 , RIG-I 29 , and TLR3 30 , major cytoplasmic nucleic acid sensors that activate the innate immune signalling pathway.…”

mentioning

confidence: 99%

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

Tanaka

Kosako

et al. 2023

Preprint

View full text Add to dashboard Cite

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.

show abstract

Proteomic analysis reveals zinc-finger CCHC-type containing protein 3 as a factor inhibiting virus infection by promoting innate signaling

Cited by 7 publications

References 30 publications

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

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

ZCCHC3 is a stress granule zinc knuckle protein that strongly suppresses LINE-1 retrotransposition

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

Contact Info

Product

Resources

About