Transcriptome Regulation by PARP13 in Basal and Antiviral States in Human Cells

Busa, Veronica F.; Ando, Yoshinari; Aigner, Stefan; Yee, Brian A.; Yeo, G; Leung, Anthony K.L.

doi:10.1101/2022.12.19.520435

Cited by 2 publications

(2 citation statements)

References 55 publications

(134 reference statements)

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“…Another study using RNA-seq identified a number of DEGs between uninfected ZAP-WT and ZAP-KO A549 cells [52]. In the most recent study, the authors demonstrated that ZAP influences hundreds of transcripts in ZAP-WT and ZAP-KO HEK cells [53]. Directly comparing the DEGs between our study and the above studies poses challenges due to variations in cell types, origins, and the employed comparative bioinformatics strategies.…”

Section: Discussionmentioning

confidence: 78%

“…Thus, our study provides the first high-throughput dataset highlighting the impact of ZAP on global gene expression during virus infection. During submission of this manuscript, a study indirectly supporting our findings was published [53]. The authors used RNA-seq in ZAP-WT and ZAP-KO HEK cells transfected with viral mimetic RNA oligos and mock transfection to normalize DEGs.…”

Section: Discussionmentioning

confidence: 82%

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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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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 82%

Endogenous ZAP is associated with altered Zika virus infection phenotype

Le,

Singh,

Sabir

et al. 2024

Preprint

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Alphavirus Evasion of Zinc Finger Antiviral Protein (ZAP) Correlates with CpG Suppression in a Specific Viral nsP2 Gene Sequence

Nguyen

Aldana

Yang

et al. 2023

Viruses

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Certain re-emerging alphaviruses, such as chikungunya virus (CHIKV), cause serious disease and widespread epidemics. To develop virus-specific therapies, it is critical to understand the determinants of alphavirus pathogenesis and virulence. One major determinant is viral evasion of the host interferon response, which upregulates antiviral effectors, including zinc finger antiviral protein (ZAP). Here, we demonstrated that Old World alphaviruses show differential sensitivity to endogenous ZAP in 293T cells: Ross River virus (RRV) and Sindbis virus (SINV) are more sensitive to ZAP than o’nyong’nyong virus (ONNV) and CHIKV. We hypothesized that the more ZAP-resistant alphaviruses evade ZAP binding to their RNA. However, we did not find a correlation between ZAP sensitivity and binding to alphavirus genomic RNA. Using a chimeric virus, we found the ZAP sensitivity determinant lies mainly within the alphavirus non-structural protein (nsP) gene region. Surprisingly, we also did not find a correlation between alphavirus ZAP sensitivity and binding to nsP RNA, suggesting ZAP targeting of specific regions in the nsP RNA. Since ZAP can preferentially bind CpG dinucleotides in viral RNA, we identified three 500-bp sequences in the nsP region where CpG content correlates with ZAP sensitivity. Interestingly, ZAP binding to one of these sequences in the nsP2 gene correlated to sensitivity, and we confirmed that this binding is CpG-dependent. Our results demonstrate a potential strategy of alphavirus virulence by localized CpG suppression to evade ZAP recognition.

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Transcriptome Regulation by PARP13 in Basal and Antiviral States in Human Cells

Cited by 2 publications

References 55 publications

Endogenous ZAP is associated with altered Zika virus infection phenotype

Endogenous ZAP is associated with altered Zika virus infection phenotype

Alphavirus Evasion of Zinc Finger Antiviral Protein (ZAP) Correlates with CpG Suppression in a Specific Viral nsP2 Gene Sequence

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