Biology subjects

Ding, C.

Publications and source records attributed to Ding, C..

5 recordsLinked to original sources

bioRxiv2018

Infectious bronchitis virus attaches to lipid rafts and enters cells via clathrin mediated endocytosis

Due to its economic importance to in poultry industry, the biology and pathogenesis of infectious bronchitis virus (IBV) have been investigated extensively. However, the molecular mechanisms involved in IBV entry are not well characterized. In this study, systematic approaches were used to dissect IBV entry process in various susceptible cells. First, we observed that lipid rafts were involved in IBV attachment. Second, low pH in intracyplasmic vesicles was required for virus entry. By using the specific clathrin mediated endocytosis (CME) inhibitor or knock down of clathrin heavy chain (CHC), we demonstrated that IBV mainly utilized the CME for its entry. Furthermore, GTPase dynamin1 was involved in virus containing vesicle scission and internalization. Surprisingly, CME adaptor Eps15 had no effect on IBV internalization. Third, the penetration of IBV into cells led to active cytoskeleton rearrangement. After internalization, virus particles moved along with the classical endosome/lysosome track, as evidenced by co-localization of R18 labeled IBV with vehicle markers Rab5/Rab7/LAMP1 along with the infection time course. Functional inactivation of Rab5 and Rab7 significantly inhibited IBV infection. VCP, a protein helps early endosome maturation, was involved virus trafficking. Finally, by using the dual R18/DiOC labeled IBV, we observed that membrane fusion with late endosome/lysosome membranes was induced between 2-3 h.p.i.. Taken together, our findings demonstrate that IBV virions attach to lipid rafts and are internalized into cells via CME, move along with early/late endosomes-lysosomes, finally fuse with late endosome-lysosome membranes, release virus genome into cytoplasm. This study provides comprehensive images of IBV attachment-internalization-trafficking-fusion steps.\n\nIMPORTANCEIBV, the avian coronavirus isolated in 1937, infects chicken and causes economic loss in poultry industry. It has been reported that the entry of IBV requires low pH. However, the molecular mechanisms underlying IBV internalization and trafficking remain to be clarified. Therefore, we employed multiple chemical and molecular approaches to dissect the entry mechanisms of IBV in susceptible cells. Our results showed IBV entry was significantly inhibited when clathrin-mediated endocytosis (CME) was blocked by chemical inhibitor or depletion of clathrin protein. Moreover, by using R18-labeled IBV, we found that IBV particles attached to lipid rafts, led to actin rearrangement, and moved along with the entire endosomal system. R18/DiOC labeling method showed that IBV fused with late endosomes or lysosomes. This is the first report to describe the entire entry process of IBV, allowing for a better understanding of the infection process of group III avian coronavirus.

microbiology↗

bioRxiv2018

Aberrant Information Transfer Interferes with Functional Axon Regeneration

Functional axon regeneration requires regenerating neurons to restore appropriate synaptic connectivity and circuit function. To model this process, we developed a single-neuron assay in C. elegans that links axon regeneration and synapse reformation with recovery of relevant behavior. After axon injury to the DA9 neuron, regeneration restores synapses to their pre-injury location. Surprisingly, presynapses also accumulate in the dendrite. Both axonal and dendritic synapses are functional. Dendritic synapses result in information misrouting that suppresses behavioral recovery. Formation of dendritic synapses is specifically dependent on dynein-mediated transport and jnk-1. However, even when information transfer is corrected, axonal synapses fail to adequately transmit information. Our study reveals unexpected plasticity during functional regeneration. Regeneration of the axon is not sufficient for the reformation of correct neuronal circuits after injury. Rather, synapse reformation and function are also key variables, and manipulation of circuit reformation improves behavioral recovery.

neuroscience↗

bioRxiv2018

CHOP and IRE1α-XBP1/JNK signaling promote Newcastle Disease Virus induced apoptosis and benefit virus proliferation

Newcastle disease virus (NDV) causes severe infectious disease in poultry, and selectively kills tumor cells by inducing apoptosis. In this report, we revealed the mechanisms underlying NDV-induced apoptosis via investigation of endoplasmic reticulum (ER) stress-related unfolded protein response (UPR) in HeLa cells. We found that NDV infection induced the expression of pro-apoptotic transcription factor CHOP via PKR-eIF2 pathway. Knock down and exogenous expression studies showed that CHOP promoted cell apoptosis by down-regulation of anti-apoptotic protein BCL-2 and MCL-1, promotion of pro-apoptotic JNK and p38 signaling, and suppression of pro-survival AKT signaling. Meanwhile, CHOP facilitated NDV proliferation. Furthermore, virus infection activated IRE1, another ER stress sensor, thereby promoting the mRNA splicing of XBP1 and resulting in the translation of transcription factor XBP1s. XBP1s entered into cell nucleus, promoted the expression of ER chaperones and components of ER associated degradation (ERAD). Exogenous expression of XBP1s helped IBV proliferation, and silence of XBP1s reduced virus proliferation. Meanwhile, exogenous expression and knock down studies demonstrated that IRE1 activated pro-apoptotic JNK signaling, promoted apoptosis and inflammation. In conclusion, our current study demonstrates that the induction of CHOP and activation of IRE1-XBP1/JNK signaling cascades promote apoptosis and benefit NDV proliferation.\n\nIMPORTANCEIt is well known that NDV kills host animal and tumor cells by inducing cell apoptosis. Although several studies investigate the apoptotic phenomena in NDV-infected tumor cells, the molecular mechanisms underlying this oncolytic virus induced apoptosis is not well understood yet. In this study, we focus on characterization of the ER stress responses in NDV-infected tumor cells, and find that virus induces apoptosis by up-regulation or activation of several unfolded protein responses (UPR) related transcription factors and signaling: such as ATF4, CHOP and XBP1s, and pro-apoptotic kinases (IRE1, JNK, p38). Moreover, activation of these transcription factors and signaling cascades helps virus proliferation. Our study dissects the UPR induced apoptosis in NDV-infected tumor cells, and provides the evidence that UPR favors NDV proliferation.

microbiology↗

bioRxiv2017

Deep Brain Stimulation for Parkinson’s disease changes perception in the Rubber Hand Illusion

Parkinsons disease (PD) alters cortico-basal ganglia-thalamic circuitry and susceptibility to an illusion of bodily awareness, the Rubber Hand Illusion (RHI). Bodily awareness is thought to result from multisensory integration in a predominantly cortical network; the role of subcortical connections is unknown. We studied the effect of modulating cortico-subcortical circuitry on multisensory integration for bodily awareness in PD patients treated with subthalamic nucleus (STN) deep brain stimulation (DBS) using the RHI experiment. Typically, synchronous visuo-tactile cues induce a false perception of touch on the rubber hand as if it were the subjects hand, whereas asynchronous visuo-tactile cues do not. However, we found that in the asynchronous condition, patients in the off-stimulation state did not reject the RHI as strongly as healthy controls; switching on STN-DBS partially normalised their responses. Patients in the off-stimulation state also misjudged the position of their hand, indicating it to be closer to the rubber hand than controls. However, STN-DBS did not affect proprioceptive judgements or subsequent arm movements altered by the perceptual effects of the illusion. Our findings support the idea that the STN and subcortical connections have a key role in multisensory integration for bodily awareness. Decisionmaking in multisensory bodily illusions is discussed.

neuroscience↗

bioRxiv2017

Intra-protein binding peptide fragments have specific and intrinsic sequence patterns

The key finding in the DNA double helix model is the specific pairing or binding between nucleotides A-T and C-G, and the pairing rules are the molecule basis of genetic code. Unfortunately, no such rules have been discovered for proteins. Here we show that similar rules and intrinsic sequence patterns between intra-protein binding peptide fragments do exist, and they can be extracted using a deep learning algorithm. Multi-millions of binding and non-binding peptide fragments from currently available protein X-ray structures are classified with an accuracy of up to 93%. This discovery has the potential in helping solve protein folding and protein-protein interaction problems, two open and fundamental problems in molecular biology.\n\nOne Sentence SummaryClassification of binding and non-binding intra-protein peptide fragments using feed-forward neural network

bioinformatics↗