African Swine Fever Virus Structural Protein p17 Inhibits Cell Proliferation through ER Stress—ROS Mediated Cell Cycle Arrest

Xia, Nengwen; Wang, Hui; Liu, Xueliang; Shao, Qi; Ao, Da; Xu, Yan; Jiang, Sheng; Luo, Jia; Zhang, Jiajia; Chen, Nanhua; Meurens, François; Zheng, Wanglong; Zhu, Jianzhong

doi:10.3390/v13010021

Cited by 38 publications

(30 citation statements)

References 40 publications

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“…ASFV p17 protein is encoded by the D117L gene and consists of 117 amino acids. There are three glycosylation sites including N12, N61 and N97, and one transmembrane domain (AAs 39-59) (23). We found that the transmembrane domain of p17 is required for interaction with STING and interference with STING in the recruitment of TBK1 and IKKε while the three glycosylation sites are not important.…”

Section: Discussionmentioning

confidence: 87%

“…The copyright holder for this preprint this version posted June 5, 2021. ; https://doi.org/10.1101/2021.06.02.446854 doi: bioRxiv preprint 4 study also indicated that p17 protein could inhibit cell proliferation by inducing cell cycle arrest via ER stress-ROS pathway (23).…”

Section: Introductionmentioning

confidence: 96%

“…P17 encoded by the ASFV D117L gene is a major structural transmembrane protein localized in the capsid and inner lipid envelope. P17 is an essential and highly abundant protein required for the assembly and maturation of the icosahedral capsid and virus viability (22,23). Several studies have indicated that the outer capsid shell was formed by the major capsid protein (p72) and four stabilizing minor proteins (H240R, M1249L, p17, p49) (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

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African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

Zheng

Xia

Luo

et al. 2021

Preprint

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African swine fever (ASF) is highly contagious, causes high mortality in domestic and feral swine, and has a significant economic impact on the global swine industry due to the lack of a vaccine or an effective treatment. African swine fever virus (ASFV) encodes more than 150 polypeptides, which may have intricate and delicate interactions with the host for the benefit of the virus to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that the p17, encoded by D117L gene could suppress porcine cGAS-STING signaling pathway, exhibiting the inhibitions of TBK1 and IRF3 phosphorylations, downstream promoter activities, cellular mRNA transcriptions and ISG56 induction, and antiviral responses. Further, we found that p17 was located in endoplasmic reticulum (ER) and Golgi apparatus, and interacted with STING, perturbing it in the recruitment of TBK1 and IKKϵ Additionally, it appeared that the transmembrane domain (amino acids 39–59) of p17 could be required for interacting with STING and inhibiting cGAS-STING pathway. Taken together, p17 could inhibit the cGAS-STING pathway through its interaction with STING and interference with STING in the recruitment of TBK1 and IKKϵ

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

Zheng

Xia

Luo

et al. 2021

Preprint

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“…First, it was evidenced by MTT assay that the maximum safety concentration of TTO was 0.063% (wt/wt), and CC50 was 0.32%. As an obligate intracellular pathogen, the proliferation of VSV strictly depends on its internal replication in living cells ( 26 ). Therefore, the level of its replication rate is an intuition index for the study of the antiviral effect of TTO.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Replication Inhibitory Effects of Tea Tree Oil on Vesicular Stomatitis Virus and Anti-inflammatory Activities in Vero Cells

Shao

Huang

2021

Front. Vet. Sci.

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Viral disease management has been proven difficult, and there are no broadly licensed vaccines or therapeutics. Vesicular stomatitis virus (VSV) is an active pathogen of wild ungulates and livestock; its infection frequently caused irreversible vesicles on the tongue or other positions, leading to enormous economic loss. Tea tree oil (TTO) has been shown to be a popular remedy for many skin diseases owing to its antibacterial, antipruritic, and anti-inflammatory effects. However, the potential effect of TTO on VSV proliferation and the corresponding inflammatory response in cells remain unclear. In this study, methyl thiazolyl tetrazolium assay was used to evaluate the cell viability of TTO, and cytotoxic concentration 50 (CC50) was calculated. Then, fluorescence observation, reverse transcription–quantitative polymerase chain reaction, Western blot (WB), and flow cytometry (FCM) assay were used to evaluate the antiviral effect of TTO against VSV under three manners of pre-infection before medication, co-administration, pretreatment before infection at safe doses to Vero cells. Meanwhile, the mRNA expressions of interleukin 8, tumor necrosis factor α, and ISG56 in cells were also detected. The results showed that the maximum safe concentration of TTO to Vero cells was 0.063% and the CC50 is 0.32%. Most notably, TTO dose-dependently inhibited the VSV GFP fluorescence generation and restrained the replication of VSV in gene and protein levels regardless of the treatment modes. Based on the results of the FCM, effective concentration 50 of TTO against VSV is 0.019%. Similarly, the mRNA expression of the above cytokines induced by viral infection was also remarkably curbed. These findings suggest that TTO emerged blocking, prophylaxis, and treatment action against VSV replication and suppressed the related inflammation in Vero cells. This study provides a novel potential for TTO fighting against viral infection and anti-inflammatory activities in Vero cells.

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“…This new method first induces a specific double-strand DNA break (DSB) by an RNA-guided nuclease, then enables genome editing by repairing DSB via either error-prone non-homologous end joining (NHEJ) or homology-directed repair (HDR). Several recombinant herpes viruses, including HSV-1, were produced using the CRISPR-Cas9 system and can be used to conduct virus-host interaction studies 9 , 10 .…”

Section: Introductionmentioning

confidence: 99%

A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

Uyar

Plante

Piret

et al. 2021

Sci Rep

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Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.

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African Swine Fever Virus Structural Protein p17 Inhibits Cell Proliferation through ER Stress—ROS Mediated Cell Cycle Arrest

Cited by 38 publications

References 40 publications

African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

Intracellular Replication Inhibitory Effects of Tea Tree Oil on Vesicular Stomatitis Virus and Anti-inflammatory Activities in Vero Cells

A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

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