Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication

Guo, Longjun; Yu, Haidong; Gu, Weihong; Luo, Xuenong; Li, Ren; Zhang, Jian; Xu, Yunfei; Yang, Lijun; Shen, Nan; Feng, Li; Wang, Yue

doi:10.1038/srep23864

Cited by 67 publications

(73 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since viral translation for replication occurs in the cytoplasm of target cells (Lee, 2015), we postulated that autophagy which removes unnecessary cytoplasmic components (Levine et al, 2011;Reggiori and Klionsky, 2002) might be a potential effective defense mechanism against PEDV. With reference to existing results showing that autophagy can restrict invasion of other viruses including Transmissible gastroenteritis coronavirus (Guo et al, 2016), HSV-1 (Yakoub and Shukla, 2015), and Rift Valley fever virus (Moy et al, 2014), we demonstrated that rapamycin treatment in porcine IECs has a protective function against PEDV through the uptake of the virus into autophagosomes at an early stage of infection. To the best of our knowledge, this study is the first to describe the defensive mechanism of autophagy against PEDV infection in porcine IECs.…”

Section: Discussionmentioning

confidence: 52%

“…In general, most studies on in vitro viral infection use infection times of 60 min (Guo et al, 2016;Shelly et al, 2009;Zhao et al, 2014). For example, Zhao et al showed a slight change in tight junction protein expression and permeability of porcine IECs, followed by a rapid recovery after 1 h of PEDV or TEGV infection (Zhao et al, 2014).…”

Section: Rapamycin Has a Protective Effect On Cell Death Induced By Lmentioning

confidence: 99%

“…Interestingly, several recent studies have shown that chemical or physiological autophagy inducers such as rapamycin, SMER28, and starvation prevent viral infections including rift valley fever virus (Moy et al, 2014), HSV-1 (Yakoub and Shukla, 2015), and transmissible gastroenteritis virus (Guo et al, 2016). However, the role of autophagy activation in the restriction of PEDV remains unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

Kim

et al. 2017

Antiviral Research

View full text Add to dashboard Cite

Porcine epidemic diarrhea virus (PEDV) invades porcine intestinal epithelial cells (IECs) and causes diarrhea and dehydration in pigs. In the present study, we showed a suppression of PEDV infection in porcine jejunum intestinal epithelial cells (IPEC-J2) by an increase in autophagy. Autophagy was activated by rapamycin at a dose that does not affect cell viability and tight junction permeability. The induction of autophagy was examined by LC3I/LC3II conversion. To confirm the autophagic-flux (entire autophagy pathway), autophagolysosomes were examined by an immunofluorescence assay. Pre-treatment with rapamycin significantly restricted not only a 1 h infection but also a longer infection (24 h) with PEDV, while this effect disappeared when autophagy was blocked. Co-localization of PEDV and autophagosomes suggests that PEDV could be a target of autophagy. Moreover, alleviation of PEDV-induced cell death in IPEC-J2 cells pretreated with rapamycin demonstrates a protective effect of rapamycin against PEDV-induced epithelial cell death. Collectively, the present study suggests an early prevention against PEDV infection in IPEC-J2 cells via autophagy that might be an effective strategy for the restriction of PEDV, and opens up the possibility of the use of rapamycin in vivo as an effective prophylactic and prevention treatment.

show abstract

Section: Discussionmentioning

confidence: 52%

Section: Rapamycin Has a Protective Effect On Cell Death Induced By Lmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

Kim

et al. 2017

Antiviral Research

View full text Add to dashboard Cite

show abstract

“…LC3-specific siRNAs (small interference RNA) (5′-GAGUGAGCUCAUCAAGAUAtt-3′) and an unrelated control siRNA (5′-UUCUCCGAACGUGUCACGUtt-3′) [30] were synthesized from GenePharma Co., Ltd., to knockdown of LC3 expression. HCT116 cells were transfected with 100 nM LC3 siRNA or nonrelated control siRNA.…”

Section: Methodsmentioning

confidence: 99%

The Protective Roles of ROS‐Mediated Mitophagy on ¹²⁵I Seeds Radiation Induced Cell Death in HCT116 Cells

Wang

Huang

et al. 2016

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

For many unresectable carcinomas and locally recurrent cancers (LRC), 125I seeds brachytherapy is a feasible, effective, and safe treatment. Several studies have shown that 125I seeds radiation exerts anticancer activity by triggering DNA damage. However, recent evidence shows mitochondrial quality to be another crucial determinant of cell fate, with mitophagy playing a central role in this control mechanism. Herein, we found that 125I seeds irradiation injured mitochondria, leading to significantly elevated mitochondrial and intracellular ROS (reactive oxygen species) levels in HCT116 cells. The accumulation of mitochondrial ROS increased the expression of HIF-1α and its target genes BINP3 and NIX (BINP3L), which subsequently triggered mitophagy. Importantly, 125I seeds radiation induced mitophagy promoted cells survival and protected HCT116 cells from apoptosis. These results collectively indicated that 125I seeds radiation triggered mitophagy by upregulating the level of ROS to promote cellular homeostasis and survival. The present study uncovered the critical role of mitophagy in modulating the sensitivity of tumor cells to radiation therapy and suggested that chemotherapy targeting on mitophagy might improve the efficiency of 125I seeds radiation treatment, which might be of clinical significance in tumor therapy.

show abstract

“…Transmissible gastroenteritis virus (TGEV) 1 , an enteropathogenic coronavirus, is an enveloped virus with a positivesense single-stranded RNA genome (1). TGEV infection can cause apoptosis, inflammation, immune response, autophagy (2)(3)(4). We reported that TGEV infection could induce cell apoptosis via mitochondria-mediated pathway and caused a decrease of mitochondrial membrane potential, implying that mitochondrial dysfunction occurs (5,6).…”

mentioning

confidence: 99%

microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection

Zhao

Song

Bai

et al. 2019

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

In BriefZhao et al. identify microRNA-222 as a mediator of mitochondrial dysfunction, THBS1, and CD47 induced during TGEV infection and showed that mi-croRNA-222 inhibits TGEV-induced mitochondrial dysfunction via targeting and downregulating CD47. Graphical Abstract Highlights• microRNA-222 attenuates TGEV-induced mitochondrial dysfunction.• microRNA-222 downregulates THBS1 and CD47.• THBS1 is the target of microRNA-222 during TGEV infection.• THBS1 and CD47 increase mitochondrial Ca 2ϩ level and reduced mitochondrial membrane potential (MMP). Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. Our previous research showed that TGEV infection could induce mitochondrial dysfunction and upregulate miR-222 level. Therefore, we presumed that miR-222 might be implicated in regulating mitochondrial dysfunction induced by TGEV infection. To verify the hypothesis, the effect of miR-222 on mitochondrial dysfunction was tested and we showed that miR-222 attenuated TGEV-induced mitochondrial dysfunction. To investigate the underlying molecular mechanism of miR-222 in TGEV-induced mitochondrial dysfunction, a quantitative proteomic analysis of PK-15 cells that were transfected with miR-222 mimics and infected with TGEV was per-formed. In total, 4151 proteins were quantified and 100 differentially expressed proteins were obtained (57 upregulated, 43 downregulated), among which thrombospondin-1 (THBS1) and cluster of differentiation 47 (CD47) were downregulated. THBS1 was identified as the target of miR-222. Knockdown of THBS1 and CD47 decreased mitochondrial Ca 2؉ level and increased mitochondrial membrane potential (MMP) level. Reversely, overexpression of THBS1 and CD47 elevated mitochondrial Ca 2؉ level and reduced mitochondrial membrane potential (MMP) level. Together, our data establish a significant role of miR-222 in regulating mitochondrial dysfunction in response to TGEV infection.

show abstract

Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication

Cited by 67 publications

References 67 publications

Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

The Protective Roles of ROS‐Mediated Mitophagy on ¹²⁵I Seeds Radiation Induced Cell Death in HCT116 Cells

microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection

Contact Info

Product

Resources

About

Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication

Cited by 67 publications

References 67 publications

Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

The Protective Roles of ROS‐Mediated Mitophagy on 125I Seeds Radiation Induced Cell Death in HCT116 Cells

microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection

Contact Info

Product

Resources

About

The Protective Roles of ROS‐Mediated Mitophagy on ¹²⁵I Seeds Radiation Induced Cell Death in HCT116 Cells