Biology subjects

Feng, P.

Publications and source records attributed to Feng, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Bacteria-herpesvirus interaction reveals a proviral role of ISGylation in promoting herpesvirus capsid assembly

Herpesviruses are common pathogens of the oral cavity, yet how they interact with other oral microbes are poorly understood. Using murine gamma-herpesvirus 68 (MHV68) as a model for human gamma-herpesviruses, we discover that ISGylation is hijacked to facilitate viral capsid assembly and lytic replication. Co-infection with the oral Aggregatibacter actinomycetemcomitans (A.a.) and MHV68 synergistically induced interferon-stimulated gene 15 (ISG15) expression and global ISGylation. Proteomic profiling revealed viral structural proteins as the dominant targets of ISGylation in MHV68-infected cells. Genetic ablation of ISGylation, using ISGylation-resistant recombinant MHV68 and ISG15-deficient mouse embryonic fibroblasts (MEFs), demonstrated that ISGylation of the major capsid protein ORF25 is required for efficient capsid assembly and maturation into the infectious C-type virions. Strikingly, introduction of a de novo ISGylation site into the ISGylation-resistant MHV68 was sufficient to restore ISGylation, capsid assembly, and virion maturation. Consistent with these findings, A.a. failed to enhance MHV68 lytic replication in ISG15-deficient MEFs. Extending this mechanism to representative herpesviruses, we showed that ISGylation of major capsid proteins is broadly required for efficient lytic replication. Together, these findings uncover a previously unrecognized strategy by which herpesviruses exploit an ISG15 innate immune effector, amplified by microbial co-infection, to promote virion biogenesis and productive infection.

microbiology↗

bioRxiv2025

A multi-tissue atlas of genetic regulatory effects in sheep

Characterizing the impact of genomic variants on genome function and ultimately complex traits in livestock is essential for the development of sustainable precision agriculture and comparative genomics. Here, as part of the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we present the pilot phase of the SheepGTEx resource through analyzing 6,761 RNA-sequencing samples of 51 primary tissues in a multi-breed population of sheep. We identify millions of regulatory variants associated with seven types of molecular phenotypes, and fine-map 322,468 primary and 114,017 non-primary effects, revealing a high degree of regulatory allelic heterogeneity. We systematically characterize the pleiotropic effects of these variants on molecular phenotypes, assess their context-specific regulatory patterns across tissues, breeds, sexes, and developmental stages, as well as explore their evolutionary constraints across mammals. Finally, we demonstrate the substantial potential of the SheepGTEx resource (https://sheepgtex.farmgtex.org), by providing examples of regulatory mechanisms underpinning 34 complex traits, population divergence between European and Asian breeds, and adaptive evolution in sheep over the past ten millennia.

genomics↗

bioRxiv2025

HSV-1 infection induces brain cofilin hyperphosphorylation in the 5xFAD Alzheimer's Disease mouse model

Alzheimers disease (AD) is a degenerative neurological disease characterized by various biological signatures, including synaptic dysfunction, {beta}-amyloid plaques, hyperphosphorylated Tau, cofilin-actin rods, and Hirano bodies, all of which are linked to the actin cytoskeleton and its regulators. Additionally, the presence of herpes simplex virus type 1 (HSV-1) in the brains of AD patients has long been suggested as a contributing factor for AD. However, mechanisms by which HSV-1 accelerates AD pathogenesis remain poorly understood. Here we report that HSV-1 infection induces hyperphosphorylation of cofilin in the brains of 5xFAD mice. Cofilin is an actin depolymerizing factor, and its S3 phosphorylation inactivates cofilins activity to depolymerize actin filaments. These findings facilitate the understanding of impacts of HSV-1 infection on the development of Alzheimers disease and have implications in AD therapeutics.

microbiology↗

bioRxiv2025

Cryo-EM structure of plant urea transporter DUR3 reveals essential role of C-terminal domain in tetramer assembly and insights into proton-coupled transport

Nitrogen pollution, caused by the overuse of nitrogen-fertilizers such as urea in agricultural production, has become a serious problem that threatens both the environment and human health. Improving the nitrogen use efficiency of crops is an important approach to reduce fertilizer use. DUR3, a high-affinity urea transporter, enables plants to acquire urea from natural or agricultural soils with low urea concentrations and has been proposed as a promising target for engineering crops to improve nitrogen-fertilizer use efficiency. Despite extensive studies for more than 20 years, the structure, substrate recognition and transport mechanism of DUR3 have remained unknown. Here we report the cryo-EM structure of maize DUR3 (ZmDUR3) at 3.41 [A] resolution. ZmDUR3 adopts an amino acid-polyamine-organocation (APC) superfamily fold and is structurally distinct from animal facilitative urea transporters. Our structure provides important insights into urea recognition by DUR3 and suggests that a pair of acidic residues is potentially involved in proton coupling during urea transport. Furthermore, our structural and functional studies indicate that DUR3 assembles into a tetramer and tetramer formation is important for its function. Our results pave the way for engineering plant DUR3 protein for applications in sustainable agricultural production.

plant biology↗

bioRxiv2024

Glutamate (E299) is a key residue in the evolutionarily divergence of the SAM-dependent methyltransferases DnrK and RdmB in anthracycline biosynthesis

A novel sub-class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines, which include antineoplastic compounds. Intriguingly, the closely related methyltransferases DnrK and RdmB have markedly divergent functions. We investigated their catalytic activities and discovered a previously unknown 10-hydroxylation activity for DnrK and 4-O-methylation activity for RdmB. Isotope-labeling demonstrated that the 10-hydroxy group introduced by DnrK is derived from water molecules while RdmB utilizes O2. A single residue, E299, was the key modulator in the differing catalytic functions of DnrK and RdmB, especially the decarboxylative oxidation activity. Furthermore, the multifunctionality of DnrK was demonstrated to be SAM-tunable and concerted, whereas RdmB activity was cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.

biochemistry↗

bioRxiv2024

A 10-valent composite mRNA vaccine against both influenza and COVID-19

The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19. Author summaryAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine showed highly effective in preclinical trials, generating strong immune responses, and ensuring protection against both matching and heterologous strains of influenza and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.

microbiology↗

bioRxiv2024

Unraveling the gut microbiota of Tibetan chickens: insights into highland adaptation and ecological advantages

Tibetan animals have several unique advantages owing to the harsh ecological conditions under which they live. Tibetan mammals have been studied extensively. However, understanding of the advantages and underlying mechanisms of the representative high-latitude bird, the Tibetan chicken (Gallus gallus, TC), remains limited. The gut microbiota of animals has been conclusively shown to be closely related to both host health and host environmental adaptation. This study aimed to explore the relationships between the cecal microbiome and the advantages of TCs based on comparisons among three populations: native TCs residing on the plateau, domestic TCs living in the plain, and one native plain species. Metatranscriptomic sequencing revealed a significant enrichment of active Bacteroidetes but a loss of active Firmicutes in native TCs. Additionally, the upregulated expression of genes in the cecal microbiome of native TCs showed enriched pathways related to energy metabolism, glycan metabolism, and the immune response. Furthermore, the expression of genes involved in the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) was upregulated in the cecal microbiome of native TCs. Data from targeted metabolomics further confirmed elevated levels of certain SCFAs and SBAs in the cecum of native TCs. Based on the multi-omics association analysis, we proposed that the higher ratio of active Bacteroidetes/Firmicutes may be attributed to the efficient energy metabolism and stronger immunological activity of native TCs. Our findings provide a better understanding of the interactions between gut microbiota and highland adaptation, and novel insights into the mechanisms by which Tibetan chickens adapt to the plateau hypoxic environment. IMPORTANCEThe composition and function of the active cecal microbiome were significantly different between the plateau Tibetan chicken population and the plain chicken population. Higher expression genes related to energy metabolism and immune response were found in the cecal microbiome of the plateau Tibetan chicken population. The cecal microbiome in the plateau Tibetan chicken population exhibited higher biosynthesis of short-chain fatty and secondary bile acids, resulting in higher cecal content of these metabolites. The active Bacteroidetes/Firmicutes ratio in the cecal microbiome may contribute to the high-altitude adaptive advantage of the plateau Tibetan chicken population.

microbiology↗

bioRxiv2023

The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection

As obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+ synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+ synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT de-phosphoribosylates viral proteins in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.

molecular biology↗

bioRxiv2023

Capturing dynamic fear experiences in naturalistic contexts: An ecologically valid fMRI signature integrating brain activation and connectivity

Enhancing our understanding of how the brain constructs conscious emotional experiences within dynamic real-life contexts necessitates ecologically valid neural models. Here, we present evidence delineating the constraints of current fMRI activation models in capturing naturalistic fear dynamics. To address this challenge, we fuse naturalistic fMRI with predictive modeling techniques to develop an ecologically valid fear signature that integrates activation and connectivity profiles, allowing for accurate prediction of subjective fear experience under highly dynamic close-to-real-life conditions. This signature arises from insights into the crucial role of distributed brain networks and their interactions in emotion modulation, and the potential of network-level information to improve predictions in dynamic contexts. Across a series of investigations, we demonstrate that this signature predicts stable and dynamic fear experiences across naturalistic scenarios with heightened sensitivity and specificity, surpassing traditional activation- and connectivity-based signatures. Notably, the integration of affective connectivity profiles enables accurate real-time predictions of fear fluctuations in naturalistic settings. Additionally, we unearth a distributed yet redundant brain-wide representation of fear experiences. Subjective fear is encoded not only by distributed cortical and subcortical regions but also by their interactions, with no single brain system conveying substantial unique information. Our study establishes a comprehensive and ecologically valid functional brain architecture for subjective fear in dynamic environments and bridges the gap between experimental neuroscience and real-life emotional experience.

neuroscience↗

bioRxiv2023

METTL16 Controls Kaposi's Sarcoma-Associated Herpesvirus Replication by Regulating S-Adenosylmethionine Cycle

Oncogenic Kaposis sarcoma-associated herpesvirus (KSHV) consists of latent and lytic replication phases, both of which are important for the development of KSHV- related cancers. As one of the most abundant RNA modifications, N6-methyladenosine (m6A) and its related complexes regulate KSHV life cycle. However, the role of METTL16, a new RNA methyltransferase, in KSHV life cycle remains unknown. In this study, we have identified a suppressive role of METTL16 in KSHV lytic replication. METTL16 knockdown increased while METTL16 overexpression reduced KSHV lytic replication. METTL16 binding to and writing of m6A on MAT2A transcript are essential for its splicing, maturation and expression. As a rate-limiting enzyme in the methionine- S-adenosylmethionine (SAM) cycle, MAT2A catalyzes the conversion of L-methionine to SAM required for the transmethylation of protein, DNA and RNA, transamination of polyamines, and transsulfuration of cystathionine. Consequently, knockdown or chemical inhibition of MAT2A reduced intracellular SAM level and enhanced KSHV lytic replication. In contrast, SAM treatment was sufficient to inhibit KSHV lytic replication and reverse the effect of the enhanced KSHV lytic program caused by METTL16 or MAT2A knockdown. Mechanistically, METTL16 or MAT2A knockdown increased while SAM treatment decreased the intracellular reactive oxygen species level by altering glutathione level, which is essential for efficient KSHV lytic replication. These findings demonstrate that METTL16 suppresses KSHV lytic replication by modulating the SAM cycle to maintain intracellular SAM level and redox homeostasis, thus illustrating the linkage of KSHV life cycle with specific m6A modifications, and cellular metabolic and oxidative conditions.

microbiology↗

bioRxiv2023

Mining multi-omics data for molecular subtyping in gliomas facilitates precise clinical treatment

Glioma is the most common malignancy in the skull, accounting for approximately 2% of adult systemic tumors. It is characterized by a high recurrence rate, high disability rate, and poor sensitivity to chemotherapy. Different subtypes of glioma exhibit varying prognosis and chemotherapy sensitivities. Currently, researchers extensively study the molecular classification of glioma based on transcriptomic features, facilitating the evaluation of prognosis. However, identification of tumor subtypes based on the single-layer-omics data have several limitations. In this regard, the present study aimed to identify new subtypes of glioma using three omics datasets for prognosis prediction. As a result, cluster A subtype was identified to be associated with lower activation of cell proliferation and better prognosis, while cluster B subtype exhibited higher infiltration of M2-type macrophages and higher activation of the epithelial-mesenchymal transition (EMT) pathway, potentially leading to a poorer prognosis. Furthermore, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm and limma R package to identify driver genes for clusters A and B. Consequently, nine genes were identified as gene signatures for cluster A. Based on this finding, we quantified the two subtypes using the single-sample gene set enrichment analysis (ssGSEA) algorithm, where a higher score were linked to elevated tumor mutation burden (TMD) and signaling pathways related to cell proliferation. Low scores indicated enrichment of tumorigenesis-related pathways and poor prognosis. In silico drug screening suggested that AGI-6780 could be an effective compound for high cluster subtypes, based on brain tumor cell lines. Consequently, our study determined that the score can serve as an effective index to predict the prognosis of glioma.

cancer biology↗

bioRxiv2022

ame-miR-34 modulates the larval body weight and immune response of Apis mellifera workers to Ascosphara apis invasion

MiRNAs are critical regulators of numerous physiological and pathological processes. Ascosphaera apis exclusively infects bee larvae and causes chalkbrood disease. However, the function and mechanism of miRNAs in the bee larval response to A. apis infection is poorly understood. Here, ame-miR-34, a previously predicted miRNA involved in the response of Apis mellifera ligustica larvae to A. apis invasion, was subjected to molecular validation, and overexpression and knockdown were then conducted to explore the regulatory functions of ame-miR-34 in larval body weight and immune response. Stem-loop RT-PCR and Sanger sequencing confirmed the authenticity of ame-miR-34 in the larval gut of A. m. ligustica. RT-qPCR results demonstrated that compared with that in the uninfected larval guts, the expression level of ame-miR-34 was significantly downregulated (P < 0.001) in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae, indicative of the remarkable suppression of host ame-miR-34 due to A. apis infection. In comparison with the corresponding negative control (NC) groups, the expression level of ame-miR-34 in the larval guts in the mimic-miR-34 group was significantly upregulated (P < 0.001), while that in the inhibi- tor-miR-34 group was significantly downregulated (P < 0.01). Similarly, effective overexpression and knockdown of ame-miR-34 were achieved. In addition, the body weights of 5- and 6-day-old larvae were significantly increased compared with those in the mimic-NC group; the weights of 5-day-old larvae in the inhibitor-miR-34 group were significantly decreased in comparison with those in the inhibitor-NC group, while the weights of 4- and 6-day-old larvae in the inhibi- tor-miR-34 group were significantly increased, indicating the involvement of ame-miR-34 in modulating larval body weight. Furthermore, the expression levels of both hsp and abct in the guts of A. apis-infected 4-, 5- and 6-day-old larvae were significantly upregulated after ame-miR-34 overexpression. In contrast, after ame-miR-34 knockdown, the expression levels of the aforementioned two key genes in the A. apis-infected 4-, 5- and 6-day-old larval guts were significantly downregu- lated. Together, the results demonstrated that effective overexpression and knockdown of ame-miR-34 in both noninfected and A. apis-infected A. m. ligustica larval guts could be achieved by the feeding method, and ame-miR-34 exerted a regulatory function in the host immune response to A. apis invasion through positive regulation of the expression of hsp and abct. Our findings not only provide a valuable reference for the functional investigation of bee larval miRNAs but also reveal the regulatory role of ame-miR-34 in A. mellifera larval weight and immune response. Additionally, the results of this study may provide a promising molecular target for the treatment of chalkbrood disease.

molecular biology↗

bioRxiv2022

Hardware-Efficient Compression of Neural Multi-Unit Activity Using Machine Learning Selected Static Huffman Encoders

Brain-machine interfaces (BMI) are tools for treating neurological disorders and motor-impairments. It is essential that the next generation of intracortical BMIs is wireless so as to remove percutaneous connections, i.e. wires, and the associated mechanical and infection risks. This is required for the effective translation of BMIs into clinical applications and is one of the remaining bottlenecks. However, due to cortical tissue thermal dissipation safety limits, the on-implant power consumption must be strictly limited. Therefore, both the neural signal processing and wireless communication power should be minimal, while the implants should provide signals that offer high behavioural decoding performance (BDP). The Multi-Unit Activity (MUA) signal is the most common signal in modern BMIs. However, with an ever-increasing channel count, the raw data bandwidth is becoming prohibitively high due to the associated communication power exceeding the safety limits. Data compression is therefore required. To meet this need, this work developed hardware-efficient static Huffman compression schemes for MUA data. Our final system reduced the bandwidth to 27 bps/channel, compared to the standard MUA rate of 1 kbps/channel. This compression is over an order of magnitude more than has been achieved before, while using only 0.96 uW/channel processing power and 246 logic cells. Our results were verified on 3 datasets and less than 1% loss in BDP was observed. As such, with the use of effective data compression, an order more of MUA channels can be fitted on-implant, enabling the next generation of high-performance wireless intracortical BMIs.

bioengineering↗

bioRxiv2021

APOBEC-mediated Editing of SARS-CoV-2 Genomic RNA Impacts Viral Replication and Fitness

During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A, APOBEC1, and APOBEC3G can edit on specific sites of SARS-CoV-2 RNA to produce C-to-U mutations. However, SARS-CoV-2 replication and viral progeny production in Caco-2 cells are not inhibited by the expression of these APOBECs. Instead, expression of wild-type APOBEC3 greatly promotes viral replication/propagation, suggesting that SARS-CoV-2 utilizes the APOBEC-mediated mutations for fitness and evolution. Unlike the random mutations, this study suggests the predictability of all possible viral genome mutations by these APOBECs based on the UC/AC motifs and the viral genomic RNA structure. One-sentence summaryEfficient Editing of SARS-CoV-2 genomic RNA by Host APOBEC deaminases and Its Potential Impacts on the Viral Replication and Emergence of New Strains in COVID-19 Pandemic

microbiology↗

bioRxiv2021

Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response. One Sentence SummaryA herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression

microbiology↗

bioRxiv2021

Golden pompano genome resource enables discovery of valuable gene determining growth traits

One important goal of fish genetic breeding is to identify valuable loci and genes that can facilitate growth and thereby productivity. Few such loci or genes have been identified in golden pompano (Trachinotus ovatus), a species of significant economic value. In this study, we produced a high-quality chromosome-level genome assembly of the golden pompano by de novo sequencing and assemblies for 2 parents and 200 F1 offspring by genome re-sequencing. We exploited these assemblies to identify loci and genes by QTL mapping, Kompetitive Allele Specific PCR (KASP) genotyping, and haplotype-based regional association analysis based on growth records of a 64 biparental and 147 individuals from a naturally occurring population. At a locus 291kb from BSNP21031, we identified a somatostatin receptor type 1-like (designated as gpsstr1) gene in which the BSNP1369 of the promoter region was highly associated with growth. Loss of sstr1a, the homolog of gpsstr1 in zebrafish, caused growth retardation. Sstr1a mediated growth via sstr2 and Wnt-gsk-3{beta} signaling pathways. Our findings provide new insights into the underlying mechanisms controlling growth. Our strategy can serve as an effective way to uncover novel genomic information and facilitate improvement of fish growth.

genomics↗

bioRxiv2021

Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection

The newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated IRF3 fails to bind the promoters of classic IRF3-responsible genes, thus muting IFN induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 deamidates IRF3 to inhibit IFN induction. Functionally, ORF7b and ORF8 activate CTPS1 to promote de novo CTP synthesis while shutting down IFN induction. De novo synthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation.

microbiology↗

bioRxiv2021

Autonomous Wireless System for Robust and Efficient Inductive Power Transmission to Multi-Node Implants

A number of recent and current efforts in brain machine interfaces are developing millimetre-sized wireless implants that achieve scalability in the number of recording channels by deploying a distributed swarm of devices. This trend poses two key challenges for the wireless power transfer: (1) the system as a whole needs to provide sufficient power to all devices regardless of their position and orientation; (2) each device needs to maintain a stable supply voltage autonomously. This work proposes two novel strategies towards addressing these challenges: a scalable resonator array to enhance inductive networks; and a self-regulated power management circuit for use in each independent mm-scale wireless device. The proposed passive 2-tier resonant array is shown to achieve an 11.9% average power transfer efficiency, with ultra-low variability of 1.77% across the network. The self-regulated power management unit then monitors and autonomously adjusts the supply voltage of each device to lie in the range between 1.7 V-1.9 V, providing both low-voltage and over-voltage protection.

bioengineering↗