Duck Hepatitis A Virus Type 1 Induces eIF2α Phosphorylation-Dependent Cellular Translation Shutoff via PERK/GCN2

Liu, Yuanzhi; Cheng, Anchun; Wang, Mingshu; Mao, Sai; Ou, Xumin; Yang, Qiao; Wu, Ying; Gao, Qun; Liu, Mafeng; Zhang, Shaqiu; Huang, Juan; Jia, Renyong; Zhu, Dekang; Chen, Shun; Zhao, Xinxin; Yu, Yanling; Liu, Yunya; Zhang, Ling; Tian, Bin; Pan, Leichang

doi:10.3389/fmicb.2021.624540

Cited by 7 publications

(6 citation statements)

References 49 publications

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“…Previous reports have demonstrated that DHAV-1 can induce increased phosphorylation of eIF2α [ 28 ]. eIF2α phosphorylation plays an important role in viral infection, related to the G0/G1 phase [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…The plasmid pCAGGS-3D-HA was constructed in a previous study [ 28 ]. Mouse anti-HA was purchased from MBL, mouse anti-β-actin antibody was purchased from TransGen Biotech, rabbit anti-VP3 antibody was prepared in our laboratory [ 29 ], and HRP-conjugated goat anti-mouse IgG and HRP-conjugated goat anti-rabbit IgG were purchased from Beyotime.…”

Section: Methodsmentioning

confidence: 99%

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Duck hepatitis A virus type 1 mediates cell cycle arrest in the S phase

Liu

Wang

et al. 2022

Virol J

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Background Duck hepatitis A virus type 1 (DHAV-1) is one of the most serious pathogens endangering the duck industry. However, there are few studies on the regulation of the cell cycle by DHAV-1. Methods In this study, flow cytometry was applied to analyze the effect of DHAV-1 infection on the cell cycle of duck embryo fibroblasts (DEFs). Subsequently, we analyzed the effects of cell cycle phases on DHAV-1 replication by real-time reverse transcriptase quantitative PCR (real-time RT-qPCR). Results Flow cytometry data analysis found that DEFs in the S phase increased by 25.85% and 54.21% at 24 h and 48 h after DHAV-1 infection, respectively. The levels of viral RNA detected by real-time RT-qPCR were higher in the DEFs with synchronization in the S phase or G0/G1 phase than in the control group. However, there was no difference in viral copy number between the G2/M phase arrest and control groups. In addition, non-structural protein 3D of DHAV-1 significantly increased cells in the S phase, indicating that 3D protein is one of the reasons for the cell cycle arrest in the S phase. Conclusions In summary, DHAV-1 infection induces the cell cycle arrest of DEFs in the S phase. Both S phase and G0/G1 phase synchronization facilitate the replication of DHAV-1, and 3D protein is one of the reasons for the S phase arrest.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Duck hepatitis A virus type 1 mediates cell cycle arrest in the S phase

Liu

Wang

et al. 2022

Virol J

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“…It is well known that protein is the material basis of life activities (63). The same protein exists in different structures and performs different biological functions due to post-translational modifications (64). Current studies have shown that the cargoes carried by MDSCs-Exos are mainly involved in the immunosuppressive effect of MDSCs (65).…”

Section: Protein Differences Between Mdscs and Their Exosomesmentioning

confidence: 99%

Roles of the Exosomes Derived From Myeloid-Derived Suppressor Cells in Tumor Immunity and Cancer Progression

Chen

Yuan

et al. 2022

Front. Immunol.

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Tumor immunity is involved in malignant tumor progression. Myeloid-derived suppressor cells (MDSCs) play an irreplaceable role in tumor immunity. MDSCs are composed of immature myeloid cells and exhibit obvious immunomodulatory functions. Exosomes released by MDSCs (MDSCs-Exos) have similar effects to parental MDSCs in regulating tumor immunity. In this review, we provided a comprehensive description of the characteristics, functions and mechanisms of exosomes. We analyzed the immunosuppressive, angiogenesis and metastatic effects of MDSCs-Exos in different tumors through multiple perspectives. Immunotherapy targeting MDSCs-Exos has demonstrated great potential in cancers and non-cancerous diseases.

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“…IRES-mediated translation initiation of viral mRNAs differs from cap-dependent translation initiation of most eukaryotic mRNAs ( Leppek et al, 2018 ). Similar to other picornaviruses, DHAV-1 can overcome the massive cellular translation block after infection, and the mechanism driven by IRES provides advantages for viral protein synthesis ( Han et al, 2021 ; Liu Y. et al, 2021 ). The activity of IRESs depends on specific viral RNA motifs, with each type sharing a common RNA structural core ( Martinez-Salas et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Specific DNAzymes cleave the 300–618 nt of 5′UTR to inhibit DHAV-1 translation and replication

Wei

Cheng

et al. 2022

Front. Microbiol.

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DNAzymes effectively inhibit the expression of viral genes. Duck hepatitis A virus type-1 (DHAV-1) genomic RNA carries an internal ribosome entry site (IRES). The IRES initiates the translation of DHAV-1 via a mechanism that differs from that of cap-dependent translation. Therefore, it is an attractive target for the treatment of DHAV-1. In this study, we designed 6 DNAzymes (Dzs) specifically targeting 300–618 nt sequence in the DHAV-1 5′untranslated region (UTR; a predicted IRES-like element). In the presence of divalent metal ions, three designed DNAzymes (DZ369, DZ454, and DZ514) efficiently cleaved the 300–618 nt sequence of the DHAV-1 5′UTR RNA. The activity of the Dzs was particularly dependent on Mg2+ ions. Subsequently, the translation inhibitory activity of these Dzs was determined by western blotting experiments. The Dzs effectively inhibited the translation mediated by the 300–618 nt of DHAV-1 5′UTR in duck embryo fibroblasts (DEFs). Importantly, DZ454 showed the strongest inhibitory effect, and its inhibition was time and dose dependent. However, none of the Dzs showed significant inhibition of cap-dependent translation. These results suggest that these Dzs show specificity for target RNA. Moreover, DZ454 inhibited the replication of DHAV-1. In conclusion, the designed DNAzymes can be used as inhibitors of DHAV-1 RNA translation and replication, providing new insights useful for the development of anti-DHAV-1 drugs.

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Duck Hepatitis A Virus Type 1 Induces eIF2α Phosphorylation-Dependent Cellular Translation Shutoff via PERK/GCN2

Cited by 7 publications

References 49 publications

Duck hepatitis A virus type 1 mediates cell cycle arrest in the S phase

Duck hepatitis A virus type 1 mediates cell cycle arrest in the S phase

Roles of the Exosomes Derived From Myeloid-Derived Suppressor Cells in Tumor Immunity and Cancer Progression

Specific DNAzymes cleave the 300–618 nt of 5′UTR to inhibit DHAV-1 translation and replication

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