Cleavage of Dicer Protein by I7 Protease during Vaccinia Virus Infection

Chen, Jhih-Si; Li, Huichun; Lin, Shu-I; Yang, Chee-Hing; Chien, Wan-Yu; Syu, Ciao-Ling; Lo, Shih-Yen

doi:10.1371/journal.pone.0120390

Cited by 15 publications

(12 citation statements)

References 45 publications

(71 reference statements)

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“…It is possible that specificity in this regard simply relates to endogenous miRNA properties in the cell but given that some miRNAs can be advantageous to viruses [ 48 ] while others broadly antiviral [ 49 ], it is hard to imagine the virus would not evolve to elicit more control over these molecules. At the same time additional reports have demonstrated that VACV also encodes mechanisms for inhibiting pre-miRNA processing [ 12 , 50 ] which could also contribute to the increase in pre-miRNA forms and reduction of mature miRNAs at late time points that we also observe. In summary this virus interfaces with host small RNA biogenesis and turn over through multiple mechanisms and the functional consequences of this merit further attention.…”

Section: Discussionsupporting

confidence: 77%

Quantitative Analysis of MicroRNAs in Vaccinia virus Infection Reveals Diversity in Their Susceptibility to Modification and Suppression

et al. 2015

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Vaccinia virus (VACV) is a large cytoplasmic DNA virus that causes dramatic alterations to many cellular pathways including microRNA biogenesis. The virus encodes a poly(A) polymerase which was previously shown to add poly(A) tails to the 3’ end of cellular miRNAs, resulting in their degradation by 24 hours post infection (hpi). Here we used small RNA sequencing to quantify the impact of VACV infection on cellular miRNAs in human cells at both early (6 h) and late (24 h) times post infection. A detailed quantitative analysis of individual miRNAs revealed marked diversity in the extent of their modification and relative change in abundance during infection. Some miRNAs became highly modified (e.g. miR-29a-3p, miR-27b-3p) whereas others appeared resistant (e.g. miR-16-5p). Furthermore, miRNAs that were highly tailed at 6 hpi were not necessarily among the most reduced at 24 hpi. These results suggest that intrinsic features of human cellular miRNAs cause them to be differentially polyadenylated and altered in abundance during VACV infection. We also demonstrate that intermediate and late VACV gene expression are required for optimal repression of some miRNAs including miR-27-3p. Overall this work reveals complex and varied consequences of VACV infection on host miRNAs and identifies miRNAs which are largely resistant to VACV-induced polyadenylation and are therefore present at functional levels during the initial stages of infection and replication.

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Section: Discussionsupporting

confidence: 77%

Quantitative Analysis of MicroRNAs in Vaccinia virus Infection Reveals Diversity in Their Susceptibility to Modification and Suppression

et al. 2015

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“…In addition to CoVs, many other virus-encoded proteases are reported to target host proteins. For example, vaccinia virus-encoded I7 protease cleaves Dicer protein to suppress microRNA (miRNA) processing (72). The leader protease of foot-and-mouth disease virus (FMDV) cleaves RNA helicase LGP2 to mediate immune evasion (73).…”

Section: Discussionmentioning

confidence: 99%

Porcine Deltacoronavirus nsp5 Cleaves DCP1A To Decrease Its Antiviral Activity

Zhu

Chen

Tian

et al. 2020

J Virol

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Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The nonstructural protein nsp5, also called 3C-like protease, is responsible for processing viral polyprotein precursors in coronavirus (CoV) replication. Previous studies have shown that PDCoV nsp5 cleaves the NF-κB essential modulator and the signal transducer and activator of transcription 2 to disrupt interferon (IFN) production and signaling, respectively. Whether PDCoV nsp5 also cleaves IFN-stimulated genes (ISGs), IFN-induced antiviral effector molecules, remains unclear. In this study, we screened 14 classical ISGs and found that PDCoV nsp5 cleaved the porcine mRNA-decapping enzyme 1a (pDCP1A) through its protease activity. Similar cleavage of endogenous pDCP1A was also observed in PDCoV-infected cells. PDCoV nsp5 cleaved pDCP1A at glutamine 343 (Q343), and the cleaved pDCP1A fragments, pDCP1A1–343 and pDCP1A344–580, were unable to inhibit PDCoV infection. Mutant pDCP1A-Q343A, which resists nsp5-mediated cleavage, exhibited a stronger ability to inhibit PDCoV infection than wild-type pDCP1A. Interestingly, the Q343 cleavage site is highly conserved in DCP1A homologs from other mammalian species. Further analyses demonstrated that nsp5 encoded by seven tested CoVs that can infect human or pig also cleaved pDCP1A and human DCP1A, suggesting that DCP1A may be the common target for cleavage by nsp5 of mammalian CoVs. IMPORTANCE Interferon (IFN)-stimulated gene (ISG) induction through IFN signaling is important to create an antiviral state and usually directly inhibits virus infection. The present study first demonstrated that PDCoV nsp5 can cleave mRNA-decapping enzyme 1a (DCP1A) to attenuate its antiviral activity. Furthermore, cleaving DCP1A is a common characteristic of nsp5 proteins from different coronaviruses (CoVs), which represents a common immune evasion mechanism of CoVs. Previous evidence showed that CoV nsp5 cleaves the NF-κB essential modulator and signal transducer and activator of transcription 2. Taken together, CoV nsp5 is a potent IFN antagonist because it can simultaneously target different aspects of the host IFN system, including IFN production and signaling and effector molecules.

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“…Plasmid construction and DNA transfection. The expression plasmids used in this study were constructed using standard protocols as described in our previous studies (37). The primer sequences used for cloning are available upon request.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-Independent Modulation of DICER1 Expression by hAgo2

Yang

et al. 2020

Molecular and Cellular Biology

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Many proteins, including DICER1 and hAgo2, are involved in the biogenesis of the microRNAs. Whether hAgo2 regulates DICER1 expression is unknown. Exogenously over-expressed hAgo2 suppressed DICER1 expression at the levels of both protein and mRNA, and the reduction in hAgo2 expression enhanced DICER1 expression. Precursor miRNA processing mediated by DICER1 was also modulated by hAgo2. However, hAgo2 protein did not suppress DICER1 promoter activity. Therefore, hAgo2 protein probably regulates DICER1 expression at the post-transcriptional level. Indeed, hAgo2 protein inhibited the reporter assay of the DICER1 mRNA 3′-UTR. Previous reports have demonstrated that miRNAs (e.g., let-7, miR-103/107) inhibited DICER1 expression post-transcriptionally. However, hAgo2 still suppressed DICER1 expression in the cells depleted of these miRNAs. Moreover, the reporter activities of DICER1 mRNA 3′-UTR without these miRNA binding sites were still suppressed by hAgo2. Therefore, in addition to a miRNA-dependent pathway, hAgo2 can also modulate DICER1 expression through a miRNA-independent mechanism. Downregulation of DICER1 expression was further proven to be dependent on both hAgo2 and AUF1 proteins. Interactions of hAgo2 and AUF1(s) proteins were demonstrated by the co-immunoprecipitation assay. As expected, hAgo2 could not suppress the DICER1 mRNA 3′-UTR reporter with a mutation in the potential AUF1-binding site. Thus, downregulation of DICER1 expression through the 3′-UTR requires both hAgo2 and AUF1.

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Cleavage of Dicer Protein by I7 Protease during Vaccinia Virus Infection

Cited by 15 publications

References 45 publications

Quantitative Analysis of MicroRNAs in Vaccinia virus Infection Reveals Diversity in Their Susceptibility to Modification and Suppression

Quantitative Analysis of MicroRNAs in Vaccinia virus Infection Reveals Diversity in Their Susceptibility to Modification and Suppression

Porcine Deltacoronavirus nsp5 Cleaves DCP1A To Decrease Its Antiviral Activity

MicroRNA-Independent Modulation of DICER1 Expression by hAgo2

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