Inhibition of Japanese encephalitis virus proliferation by long non-coding RNA SUSAJ1 in PK-15 cells

Zhou, Xiao‐Long; Yuan, Qiongyu; Zhang, Chen; Dai, Zhenglie; Du, Chengtao; Wang, Han; Li, Xiangchen; Yang, Songbai; Zhao, Ayong

doi:10.1186/s12985-021-01492-5

Cited by 11 publications

(8 citation statements)

References 63 publications

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“…Japanese encephalitis (JE), a serious vector-borne viral infection caused by the Japanese encephalitis virus (JEV), is responsible for causing Epidemic encephalitis B—an acute infectious disease of the central nervous system, in 24 countries of Southeast Asia and the Western Pacific 1 – 3 . As the transmission of JE is highly dynamic, several studies have reported substantial variation in the estimation of its global impact.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

Dwivedi¹,

Singh

El-Kafraway

et al. 2021

Sci Rep

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Japanese encephalitis (JE) virus is a flavivirus causing encephalitis causing neurological damage. RNA-dependent-RNA-polymerase (RdRp) is responsible for genome replication making it excellent anti-viral target. In this study, the crystal structure of JE RdRp (jRdRp) and bioflavonoids reported in Azadirachta indica were retrieved from specific databases. Structure-based virtual screening was employed using MTiOpenScreen server and top four compounds selected with the most negative docking scores. Conformations were redocked using AutoDock Vina; these complexes showed mechanistic interactions with Arg474, Gly605, Asp668, and Trp800 residues in the active site of jRdRp, i.e., guanosine-5′-triphosphate. Furthermore, 100 ns classical molecular dynamics simulation and binding free energy calculation showed stability of docked bioflavonoids in the active jRdRp pocket and significant contribution of van-der-Waals interactions for docked complex stability during simulation. Therefore, this study predicted the anti-viral activity of Gedunin, Nimbolide, Ohchinin acetate, and Kulactone against jRdRp and can be considered for further antiviral drug development.

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Section: Introductionmentioning

confidence: 99%

Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

Dwivedi¹,

Singh

El-Kafraway

et al. 2021

Sci Rep

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“…Avian skeletal muscle growth is comprised of distinct and precisely regulated periods of embryonic and post-hatch muscle development [52]. Studies have shown that lncRNA and miRNA expression is usually tissue specific or affects specific developmental stages [53,54]. Therefore, we questioned whether the function of the constructed ceRNA network possesses development specific to regulating pigeon muscle development.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals a lncRNA–miRNA–mRNA Network Associated with Pigeon Skeletal Muscle Development

Zhang

Chen

Han³

et al. 2021

Genes

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Growing evidence has demonstrated the emerging role of long non-coding RNA as competitive endogenous RNA (ceRNA) in regulating skeletal muscle development. However, the mechanism of ceRNA regulated by lncRNA in pigeon skeletal muscle development remains unclear. To reveal the function and regulatory mechanisms of lncRNA, we first analyzed the expression profiles of lncRNA, microRNA (miRNA), and mRNA during the development of pigeon skeletal muscle using high-throughput sequencing. We then constructed a lncRNA–miRNA–mRNA ceRNA network based on differentially expressed (DE) lncRNAs, miRNAs, and mRNAs according to the ceRNA hypothesis. Functional enrichment and short time-series expression miner (STEM) analysis were performed to explore the function of the ceRNA network. Hub lncRNA–miRNA–mRNA interactions were identified by connectivity degree and validated using dual-luciferase activity assay. The results showed that a total of 1625 DE lncRNAs, 11,311 DE mRNAs, and 573 DE miRNAs were identified. A ceRNA network containing 9120 lncRNA–miRNA–mRNA interactions was constructed. STEM analysis indicated that the function of the lncRNA-associated ceRNA network might be developmental specific. Functional enrichment analysis identified potential pathways regulating pigeon skeletal muscle development, such as cell cycle and MAPK signaling. Based on the connectivity degree, lncRNAs TCONS_00066712, TCONS_00026594, TCONS_00001557, TCONS_00001553, and TCONS_00003307 were identified as hub genes in the ceRNA network. lncRNA TCONS_00026594 might regulate the FSHD region gene 1 (FRG1)/ SRC proto-oncogene, non-receptor tyrosine kinase (SRC) by sponge adsorption of cli-miR-1a-3p to affect the development of pigeon skeletal muscle. Our findings provide a data basis for in-depth elucidation of the lncRNA-associated ceRNA mechanism underlying pigeon skeletal muscle development.

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“…PK15 cells were seeded on plates for 24 h. When the cell growth density reached 80-90%, using Lipofectamine 3000 (Invitrogen, USA), 2 µg pcDNA 3.1 lncRNA-SUSAJ1 (the sequence of lncRNA-SUSAJ1 can be found in Supplementary file) or empty plasmid (negative con-trol; NC) was transfected into each well in accordance with the manufacturer's instructions. Short interfering RNAs (siRNA) targeting lncRNA-SUSAJ1 was transfected along with si-NC and antisense oligonucleotides (ASO) [28] at a final concentration of 100 nM per well. JEV was used to infect the cells at 6 h after transfection.…”

Section: Transfectionmentioning

confidence: 99%

LncRNA-SUSAJ1 Activates the ER Stress Pathway Inhibiting JEV Proliferation by Promoting PK15 Cells Apoptosis

Yuan¹,

Fan²,

Wang³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Epidemic encephalitis B is a common zoonosis that threatens both pigs and humans. Effective prevention and control of epidemic encephalitis B is difficult. The cellular defence mechanism is closely related to the body's resistance to viral invasion. Long non-coding RNAs (lncRNAs) are involved in regulating various cellular activities. We previously found that lncRNA-SUSAJ1 could inhibit the proliferation of Japanese encephalitis virus (JEV). However, the mechanism underlying this suppression remains unclear. Methods: We performed Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-qPCR) analyses, as well as mitochondrial membrane potential, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), RNA pull-down, and RNA immunoprecipitation assays. Results: JC-1 cationic dye staining showed that lncRNA-SUSAJ1 promoted the depolarisation of mitochondrial membrane potential; H2DCFDA probe staining showed that lncRNA-SUSAJ1 enhanced the level of reactive oxygen species in PK15 porcine kidney cells. qRT-PCR and Western blotting revealed the expression levels of associated mRNAs and proteins, and the TUNEL and flow cytometry assays detected cell apoptosis. Their results showed that lncRNA-SUSAJ1 promoted the expression of pro-apoptotic genes and inhibited the expression of anti-apoptotic genes. RNA pull-down experiments using biotin-labelled lncRNA-SUSAJ1 showed colocalisation between lncRNA-SUSAJ1 and the 70 kDa heat shock protein (Hsp70). lncRNA-SUSAJ1 also activated unfolded protein response-related pathways, regulated protein degradation, and promoted apoptosis via the endoplasmic reticulum stress response, thereby inhibiting viral replication. Conclusions: The findings of this study provide insight into the specific molecular mechanism of lncRNA-SUSAJ1 resistance to viral proliferation by promoting cell apoptosis, clarify the antiviral effect of lncRNA-SUSAJ1 on JEV.

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Inhibition of Japanese encephalitis virus proliferation by long non-coding RNA SUSAJ1 in PK-15 cells

Cited by 11 publications

References 63 publications

Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

Mechanistic insights into the Japanese encephalitis virus RNA dependent RNA polymerase protein inhibition by bioflavonoids from Azadirachta indica

Integrated Analysis Reveals a lncRNA–miRNA–mRNA Network Associated with Pigeon Skeletal Muscle Development

LncRNA-SUSAJ1 Activates the ER Stress Pathway Inhibiting JEV Proliferation by Promoting PK15 Cells Apoptosis

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