Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway

Hu, Boli; Zhang, Yina; Jia, Lianshun; Wu, Huansheng; Fan, Chengfei; Sun, Yuhua; Ye, Chengjin; Liao, Min; Zhou, Jiyong

doi:10.1080/15548627.2015.1017184

Cited by 105 publications

(104 citation statements)

References 58 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…Inhibition of the PI3K/Akt/mTOR pathway can induce pro-autophagic activity. In agreement with a recent report regarding IBDV-infected DF1 cells [26], there may be a link between the activation of autophagy and the MTOR signaling pathway in vvIBDV-infected DT40 cells. An essential autophagy protein, Beclin-1 [27–30], exhibited a 2.25-fold increase at 12 h pi and remained upregulated to similar levels at 18 h pi; upregulation of Bcl-2, an anti-apoptotic protein that can inhibit the activation of pro-apoptotic proteins, was also observed at both the these time points.…”

Section: Discussionsupporting

confidence: 93%

Transcriptional profiles in bursal B-lymphoid DT40 cells infected with very virulent infectious bursal disease virus

Quan¹,

Zhu

et al. 2017

Virol J

View full text Add to dashboard Cite

BackgroundInfectious bursal disease virus (IBDV) causes a highly contagious, immunosuppressive disease in chickens. The virus mainly infects immature B lymphocytes in the bursa of Fabricius (BF). Chicken B cell line DT40, an avian leukosis virus-induced B cell line, supports very virulent IBDV (vvIBDV) infection in vitro and thereby serves as a good model for investigating the infection and pathogenesis of this virus. However, a transcriptome-wide understanding of the interaction between vvIBDV and B cells has not yet been achieved. This study aimed to employ time-course DNA microarrays to investigate gene expression patterns in DT40 cells after infection with vvIBDV strain LX.ResultsDT40 cells infected with vvIBDV exhibited alterations in the expression of many important host genes involved in signal transduction pathways, including MAPK signaling, PI3K/mTOR signaling, cell death and survival, BCR signaling, and antigen presentation. The changes in cellular mRNA levels identified by microarray analysis were confirmed for 8 selected genes using real-time reverse transcription-PCR. The upregulation of inflammatory cytokines and Toll-like receptors (TLRs) in the bursa of vvIBDV-infected chickens might involve excessive activation of the innate immune and inflammatory responses and contribute to tissue damage.ConclusionsThe present study is the first to provide a comprehensive differential transcriptional profile of cultured DT40 cells in response to vvIBDV infection and further extends our understanding of the molecular mechanisms underlying vvIBDV infection and pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 93%

Transcriptional profiles in bursal B-lymphoid DT40 cells infected with very virulent infectious bursal disease virus

Quan¹,

Zhu

et al. 2017

Virol J

View full text Add to dashboard Cite

show abstract

“…The kinase mTOR, which is a key regulator of autophagy induction [21], plays an important role in the progress of autophagy. When mTOR is inhibited (AMPK and p53 signaling), autophagy is induced.…”

Section: Resultsmentioning

confidence: 99%

Myocardial Ischemic Postconditioning Promotes Autophagy against Ischemia Reperfusion Injury via the Activation of the nNOS/AMPK/mTOR Pathway

Hao

Zhu

et al. 2017

IJMS

View full text Add to dashboard Cite

Autophagy participates in the progression of many diseases, comprising ischemia/ reperfusion (I/R). It is reported that it is involved in the protective mechanism of ischemic postconditioning (IPostC). According to research, neuronal nitric oxide synthase (nNOS) is also involved in the condition of I/R and IPostC. However, the relationship between nNOS, autophagy and IPostC has not been previously investigated. We hypothesize that IPostC promotes autophagy activity against I/R injury partially through nNOS-mediated pathways. Mouse hearts were subjected to I/R injury through the ligation of the left anterior descending coronary artery. H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, restored nNOS activity, increased the formation of autophagosome and restored the impaired autophagic flux, thus autophagic activity was raised markedly. IPostC increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and suppressed mammalian target of rapamycin (mTOR), but a selective nNOS inhibitor abolished those effects. Similar effects of IPostC were demonstrated in H9c2 cells in vitro. IPostC decreased infarct size and preserved most of the normal structure. The level of reactive oxygen species (ROS) and cell apoptosis were reduced by IPostC with improved cell viability and mitochondrial membrane potential. However, an autophagy inhibitor suppressed the protective effects. These results suggest that IPostC promoted autophagy against I/R injury at least partially via the activation of nNOS/AMPK/mTOR pathway.Keywords: ischemic postconditioning (IPostC); ischemia/reperfusion; autophagy; neuronal nitric oxide synthase (nNOS); adenosine monophosphate-activated protein kinase (AMPK); mammalian target of rapamycin (mTOR)

show abstract

“…However, at this point it is difficult to envisage a process allowing the incorporation of naked IBDV particles into the lumen of endocytic vesicles. Concerning the autophagy pathway, it has been recently published that the interaction of IBDV particles with one of the described IBDV virus receptors, HSP90AA1 (heat shock protein 90 kDa α class A member 1), causes the inactivation of the AKT-mTOR pathway, triggering a transient autophagic response in infected cells [35]. This observation suggests the possibility that IBDV might subvert the autophagy pathway in order to promote virus release.…”

Section: Discussionmentioning

confidence: 99%

Non-Lytic Egression of Infectious Bursal Disease Virus (IBDV) Particles from Infected Cells

et al. 2017

View full text Add to dashboard Cite

Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is responsible for a devastating immunosuppressive disease affecting juvenile domestic chickens. IBDV particles are naked icosahedrons enclosing a bipartite double-stranded RNA genome harboring three open reading frames (ORF). One of these ORFs codes for VP5, a non-structural polypeptide dispensable for virus replication in tissue culture but essential for IBDV pathogenesis. Using two previously described recombinant viruses, whose genomes differ in a single nucleotide, expressing or not the VP5 polypeptide, we have analyzed the role of this polypeptide during the IBDV replication process. Here, we show that VP5 is not involved in house-keeping steps of the virus replication cycle; i.e. genome transcription/replication, protein translation and virus assembly. Although infection with the VP5 expressing and non-expressing viruses rendered similar intracellular infective progeny yields, striking differences were detected on the ability of their progenies to exiting infected cells. Experimental data shows that the bulk of the VP5-expressing virus progeny efficiently egresses infected cells during the early phase of the infection, when viral metabolism is peaking and virus-induced cell death rates are as yet minimal, as determined by qPCR, radioactive protein labeling and quantitative real-time cell death analyses. In contrast, the release of the VP5-deficient virus progeny is significantly abridged and associated to cell death. Taken together, data presented in this report show that IBDV uses a previously undescribed VP5-dependent non-lytic egress mechanism significantly enhancing the virus dissemination speed. Ultrastructural analyses revealed that newly assembled IBDV virions associate to a vesicular network apparently facilitating their trafficking from virus assembly factories to the extracellular milieu, and that this association requires the expression of the VP5 polypeptide.

show abstract

Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway

Cited by 105 publications

References 58 publications

Transcriptional profiles in bursal B-lymphoid DT40 cells infected with very virulent infectious bursal disease virus

Transcriptional profiles in bursal B-lymphoid DT40 cells infected with very virulent infectious bursal disease virus

Myocardial Ischemic Postconditioning Promotes Autophagy against Ischemia Reperfusion Injury via the Activation of the nNOS/AMPK/mTOR Pathway

Non-Lytic Egression of Infectious Bursal Disease Virus (IBDV) Particles from Infected Cells

Contact Info

Product

Resources

About