Author response: KHNYN is essential for the zinc finger antiviral protein (ZAP) to restrict HIV-1 containing clustered CpG dinucleotides

Ficarelli, Mattia; Wilson, Harry; Galão, Rui Pedro; Mazzon, Michela; Antzin-Anduetza, Irati; Marsh, Mark; Neil, Stuart; Swanson, Chad M.

doi:10.7554/elife.46767.022

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Endogenous ZAP affects Zika virus RNA interactome

Sabir,

Le,

Singh

et al. 2024

RNA Biology

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Endogenous ZAP affects Zika virus RNA interactome

Sabir,

Le,

Singh

et al. 2024

RNA Biology

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The Zinc Finger Antiviral Protein restricts SARS-CoV-2

Nchioua

Mueller²,

Conzelmann

et al. 2020

Preprint

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1Recent evidence shows that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 2 is highly sensitive to interferons (IFNs). However, the underlying antiviral effectors remain to be 3 defined. Here, we show that Zinc finger antiviral protein (ZAP) that specifically targets CpG 4 dinucleotides in viral RNA sequences restricts SARS-CoV-2. We demonstrate that ZAP and its 5 cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II and III IFNs all 6 strongly inhibited SARS-CoV-2 and further induced ZAP expression. Strikingly, SARS-CoV-2 and 7 its closest relatives from bats show the strongest CpG suppression among all known human and bat 8 coronaviruses, respectively. Nevertheless, knock-down of ZAP significantly increased SARS-CoV-9 2 production in lung cells, particularly upon treatment with IFN- or IFN-. Thus, our results 10 identify ZAP as an effector of the IFN response against SARS-CoV-2, although this pandemic 11 pathogen may be preadapted to the low CpG environment in humans. 12 13 Highlights 14  SARS-CoV-2 and its closest bat relatives show strong CpG suppression 15  IFN-β, - and - inhibit SARS-CoV-2 with high efficiency 16  ZAP restricts SARS-CoV-2 and contributes to the antiviral effect of IFNs 17 18 3

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Endogenous ZAP is associated with altered Zika virus infection phenotype

Le,

Singh,

Sabir

et al. 2024

Preprint

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The zinc finger antiviral protein 1 (ZAP) has broad antiviral activity. Previous RNA-seq analyses were conducted in uninfected wild-type and ZAP-KO cells; however, the impact of ZAP on global gene expression during virus infection remains unknown. Here, we characterized global cellular gene expression in uninfected and Zika virus-infected wild-type and ZAP knockout VERO cells. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN antiviral response. We found that ZAP was associated with the inhibition of Zika virus in the absence of a robust type I IFN system (VERO cells are deficient for IFN-alpha and -beta). Also, during Zika infection in VERO cells endogenous ZAP was associated with amplification of global transcriptional antiviral responses in the absence of a robust type I IFN system. Further studies are warranted to elucidate this type I IFN-independent antiviral activity directly or indirectly mediated by ZAP.

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Author response: KHNYN is essential for the zinc finger antiviral protein (ZAP) to restrict HIV-1 containing clustered CpG dinucleotides

Cited by 4 publications

References 0 publications

Endogenous ZAP affects Zika virus RNA interactome

Endogenous ZAP affects Zika virus RNA interactome

The Zinc Finger Antiviral Protein restricts SARS-CoV-2

Endogenous ZAP is associated with altered Zika virus infection phenotype

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