Host Signal Research Articles

MicroRNA expression and analysis of immune-related putative target genes in ISKNV-infected spleen of mandarin fish (Siniperca chuatsi)

Infectious spleen and kidney necrosis virus (ISKNV), a highly infectious and lethal pathogen of mandarin fish (Siniperca chuatsi), has resulted in major aquaculture losses over the past few decades. A lack of understanding of the regulatory mechanism of viral infection has impeded the development of effective measures to control ISKNV infection. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate the processes of viral infection and are involved in various physiological processes in vivo. In this study, miRNAs involved in the response of mandarin fish to ISKNV infection were identified at several time points following infection through Illumina high-throughput sequencing. A total of 434 (27 known and 407 novel) miRNAs were identified in mandarin fish; 26 (26 up-regulated), 38 (30 up-regulated, 8 down-regulated), and 18 (14 up-regulated and 4 down-regulated) differentially expressed miRNAs (DEMs) were identified at 12, 24, and 48 h post-infection (hpi), respectively. The putative target genes of DEMs were all significantly enriched in host immune response or signaling pathways, such as autophagy, endocytosis, phosphatidylinositol signaling system, Salmonella infection, cell cycle, protein export, and protein processing in endoplasmic reticulum pathway at 12 and 24 hpi and in vascular endothelial growth factor, phosphatidylinositol signaling system and lysosome at 48 hpi. Further analysis indicated that the targeted mRNAs of miRNAs were involved in innate immunity; autophagy and endocytosis might play an important role in immune regulation within 24 hpi with ISKNV. Although the number of DEMs was lowest at 48 hpi, they might still be involved in immunity through the above pathway. We also constructed a miRNA–mRNA targeting network. Generally, the findings of this study provide novel information that advance our understanding of the regulatory mechanisms of miRNA during ISKNV infection in mandarin fish as well as the development of new approaches for preventing ISKNV infection.

A kinase-independent function of PAK is crucial for pathogen-mediated actin remodelling.

The p21-activated kinase (PAK) family regulate a multitude of cellular processes, including actin cytoskeleton remodelling. Numerous bacterial pathogens usurp host signalling pathways that regulate actin reorganisation in order to promote Infection. Salmonella and pathogenic Escherichia coli drive actin-dependent forced uptake and intimate attachment respectively. We demonstrate that the pathogen-driven generation of both these distinct actin structures relies on the recruitment and activation of PAK. We show that the PAK kinase domain is dispensable for this actin remodelling, which instead requires the GTPase-binding CRIB and the central poly-proline rich region. PAK interacts with and inhibits the guanine nucleotide exchange factor β-PIX, preventing it from exerting a negative effect on cytoskeleton reorganisation. This kinase-independent function of PAK may be usurped by other pathogens that modify host cytoskeleton signalling and helps us better understand how PAK functions in normal and diseased eukaryotic cells.

Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia

The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility to Klebsiella pneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia.

Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.

Human cytomegalovirus (HCMV) microRNAs (miRNAs) significantly rewire host signaling pathways to support the viral lifecycle and regulate host cell responses. Here we show that SMAD3 expression is regulated by HCMV miR-UL22A and contributes to the IRF7-mediated induction of type I IFNs and IFN-stimulated genes (ISGs) in human fibroblasts. Addition of exogenous TGFβ interferes with the replication of a miR-UL22A mutant virus in a SMAD3-dependent manner in wild type fibroblasts, but not in cells lacking IRF7, indicating that downregulation of SMAD3 expression to limit IFN induction is important for efficient lytic replication. These findings uncover a novel interplay between SMAD3 and innate immunity during HCMV infection and highlight the role of viral miRNAs in modulating these responses.

Mucin Msb2 cooperates with the transmembrane protein Sho1 in various plant surface signal sensing and pathogenic processes in the poplar anthracnose fungus Colletotrichum gloeosporioides.

Colletotrichum gloeosporioides is a hemibiotrophic ascomycete fungus that causes anthracnose on numerous plants worldwide and forms a specialized infection structure known as an appressorium in response to various plant surface signals. However, the associated mechanism of host surface signal recognition remains unclear. In the present study, three putative sensors, namely the mucin Msb2, the membrane sensor protein Sho1, and the G‐protein‐coupled receptor Pth11, were identified and characterized. The results showed that CgMsb2 plays a major role in the recognition of various host surface signals; deletion of CgMsb2 resulted in significant defects in appressorium formation, appressorium penetration, cellophane membrane penetration, and pathogenicity. CgSho1 plays a minor role and together with CgMsb2 cooperatively regulates host signal recognition, cellophane membrane penetration, and pathogenicity; deletion of CgSho1 resulted in an expansion defect of infection hyphae. Deletion of CgPth11 in wildtype, ΔCgMsb2, and ΔCgSho1 strains only resulted in a slight defect in appressorium formation at the early stage, and CgPth11 was dispensable for penetration and pathogenicity. However, exogenous cAMP failed to restore the defect of appressorium formation in ΔCgPth11 at the early stage. CgMsb2 contributed to the phosphorylation of the mitogen‐activated protein kinase CgMk1, which is essential for infection‐associated functions, while CgSho1 was unable to activate CgMk1 alone but rather cooperated with CgMsb2 to activate CgMk1. These data suggest that CgMsb2 contributes to the activation of CgMk1 and has overlapping functions with CgSho1 in plant surface sensing, appressorium formation, and pathogenicity.

Pixel steganography method for grayscale image steganography on colour images

The process of hiding secret data within a host signal is known as steganography; its design parameters are imperceptibility, concealment capacity, and recovered data quality. A case of images, one of the existing methods based on modification of the host image pixels is called Block Pixel Hiding Method (BPHM), which has good imperceptibility and high-capacity concealment but does not guarantee the quality of the secret image recovered. This article proposes a method that improves results BPHM based on band selection and search algorithm global called Improved Pixel Hiding Method (IPHM). According to the simulations carried out, the results obtained with IPHM are better than those obtained with BPHM. They are similar to one of the more popular methods in imaging steganography known as Quantization Index Modulation (QIM). Steganography is the method of hiding hidden data within a host signal, with imperceptibility, concealment capacity, and retrieved data quality as design criteria. In the case of images, Block Pixel Hiding Method (BPHM) is one of the available methods based on modifying the host picture pixels, which has good imperceptibility and high-capacity concealment but does not guarantee the quality of the hidden picture recovered. Improved Pixel Hiding Method is a method proposed in this article that improves BPHM outcomes by using band selection and a global search algorithm (IPHM). The results obtained using IPHM are better than those achieved with BPHM, according to simulations. They're related to Quantization Index Modulation, which is one of the most widely used picture steganography techniques (QIM).

Reactivity of Thiol-Rich Zn Sites in Diacylglycerol-Sensing PKC C1 Domain Probed by NMR Spectroscopy.

Conserved homology 1 (C1) domains are peripheral zinc finger domains that are responsible for recruiting their host signaling proteins, including Protein Kinase C (PKC) isoenzymes, to diacylglycerol-containing lipid membranes. In this work, we investigated the reactivity of the C1 structural zinc sites, using the cysteine-rich C1B regulatory region of the PKCα isoform as a paradigm. The choice of Cd2+ as a probe was prompted by previous findings that xenobiotic metal ions modulate PKC activity. Using solution NMR and UV-vis spectroscopy, we found that Cd2+ spontaneously replaced Zn2+ in both structural sites of the C1B domain, with the formation of all-Cd and mixed Zn/Cd protein species. The Cd2+ substitution for Zn2+ preserved the C1B fold and function, as probed by its ability to interact with a potent tumor-promoting agent. Both Cys3His metal-ion sites of C1B have higher affinity to Cd2+ than Zn2+, but are thermodynamically and kinetically inequivalent with respect to the metal ion replacement, despite the identical coordination spheres. We find that even in the presence of the oxygen-rich sites presented by the neighboring peripheral membrane-binding C2 domain, the thiol-rich sites can successfully compete for the available Cd2+. Our results indicate that Cd2+ can target the entire membrane-binding regulatory region of PKCs, and that the competition between the thiol- and oxygen-rich sites will likely determine the activation pattern of PKCs.

Structural Investigation of Orf Virus Bcl-2 Homolog ORFV125 Interactions with BH3-Motifs from BH3-Only Proteins Puma and Hrk.

Numerous viruses have evolved sophisticated countermeasures to hijack the early programmed cell death of host cells in response to infection, including the use of proteins homologous in sequence or structure to Bcl-2. Orf virus, a member of the parapoxviridae, encodes for the Bcl-2 homolog ORFV125, a potent inhibitor of Bcl-2-mediated apoptosis in the host. ORFV125 acts by directly engaging host proapoptotic Bcl-2 proteins including Bak and Bax as well as the BH3-only proteins Hrk and Puma. Here, we determined the crystal structures of ORFV125 bound to the BH3 motif of proapoptotic proteins Puma and Hrk. The structures reveal that ORFV125 engages proapoptotic BH3 motif peptides using the canonical ligand binding groove. An Arg located in the structurally equivalent BH1 region of ORFV125 forms an ionic interaction with the conserved Asp in the BH3 motif in a manner that mimics the canonical ionic interaction seen in host Bcl-2:BH3 motif complexes. These findings provide a structural basis for Orf virus-mediated inhibition of host cell apoptosis and reveal the flexibility of virus encoded Bcl-2 proteins to mimic key interactions from endogenous host signalling pathways.

Varicella-zoster virus early infection but not complete replication is required for the induction of chronic hypersensitivity in rat models of postherpetic neuralgia.

Herpes zoster, the result of varicella-zoster virus (VZV) reactivation, is frequently complicated by difficult-to-treat chronic pain states termed postherpetic neuralgia (PHN). While there are no animal models of VZV-induced pain following viral reactivation, subcutaneous VZV inoculation of the rat causes long-term nocifensive behaviors indicative of mechanical and thermal hypersensitivity. Previous studies using UV-inactivated VZV in the rat model suggest viral gene expression is required for the development of pain behaviors. However, it remains unclear if complete infection processes are needed for VZV to induce hypersensitivity in this host. To further assess how gene expression and replication contribute, we developed and characterized three replication-conditional VZV using a protein degron system to achieve drug-dependent stability of essential viral proteins. Each virus was then assessed for induction of hypersensitivity in rats under replication permissive and nonpermissive conditions. VZV with a degron fused to ORF9p, a late structural protein that is required for virion assembly, induced nocifensive behaviors under both replication permissive and nonpermissive conditions, indicating that complete VZV replication is dispensable for the induction of hypersensitivity. This conclusion was confirmed by showing that a genetic deletion recombinant VZV lacking DNA packaging protein ORF54p still induced prolonged hypersensitivities in the rat. In contrast, VZV with a degron fused to the essential IE4 or IE63 proteins, which are involved in early gene regulation of expression, induced nocifensive behaviors only under replication permissive conditions, indicating importance of early gene expression events for induction of hypersensitivity. These data establish that while early viral gene expression is required for the development of nocifensive behaviors in the rat, complete replication is dispensable. We postulate this model reflects events leading to clinical PHN, in which a population of ganglionic neurons become abortively infected with VZV during reactivation and survive, but host signaling becomes altered in order to transmit ongoing pain.

Reprogramming of the wheat transcriptome in response to infection with Claviceps purpurea, the causal agent of ergot

BackgroundErgot, caused by the fungal pathogen Claviceps purpurea, infects the female flowers of a range of cereal crops, including wheat. To understand the interaction between C. purpurea and hexaploid wheat we undertook an extensive examination of the reprogramming of the wheat transcriptome in response to C. purpurea infection through floral tissues (i.e. the stigma, transmitting and base ovule tissues of the ovary) and over time.ResultsC. purpurea hyphae were observed to have grown into and down the stigma at 24 h (H) after inoculation. By 48H hyphae had grown through the transmitting tissue into the base, while by 72H hyphae had surrounded the ovule. By 5 days (D) the ovule had been replaced by fungal tissue. Differential gene expression was first observed at 1H in the stigma tissue. Many of the wheat genes differentially transcribed in response to C. purpurea infection were associated with plant hormones and included the ethylene (ET), auxin, cytokinin, gibberellic acid (GA), salicylic acid and jasmonic acid (JA) biosynthetic and signaling pathways. Hormone-associated genes were first detected in the stigma and base tissues at 24H, but not in the transmitting tissue. Genes associated with GA and JA pathways were seen in the stigma at 24H, while JA and ET-associated genes were identified in the base at 24H. In addition, several defence-related genes were differential expressed in response to C. purpurea infection, including antifungal proteins, endocytosis/exocytosis-related proteins, NBS-LRR class proteins, genes involved in programmed cell death, receptor protein kinases and transcription factors. Of particular interest was the identification of differential expression of wheat genes in the base tissue well before the appearance of fungal hyphae, suggesting that a mobile signal, either pathogen or plant-derived, is delivered to the base prior to colonisation.ConclusionsMultiple host hormone biosynthesis and signalling pathways were significantly perturbed from an early stage in the wheat – C. purpurea interaction. Differential gene expression at the base of the ovary, ahead of arrival of the pathogen, indicated the potential presence of a long-distance signal modifying host gene expression.

Steganography algorithm for reversible data hiding using LSB and reversible image transformation

We present another reversible (lossless) information stowing away (inserting) strategy that takes into consideration careful recuperation of the first host signal after the implanted data is separated. The information installing approach is proposed as a speculation of the notable LSB (least significant cycle) update, which includes extra working focuses the limit contortion bend. Compacting portions of the sign that are helpless against installing spillage and dispersing these packed subtleties as a feature of the inserted payload considers lossless recovery of the first. The pressure effectiveness and in this manner the lossless information implanting capacity of a forecast based restrictive entropy coder that utilizes static segments of the host as side-data improves.

Abstract 1686: Host intrinsic STING is a promising biomarkerfor predicting clinical efficacy of anti-PD-1 inhibitors in lung cancer

Abstract Background: The stimulator of IFN genes (STING) signaling pathway plays an important role in anti-tumor immune responses. However, the mechanistic contribution of host and tumor STING signaling to the therapeutic efficacy of anti-PD-1 inhibitors in lung cancer remains unknown. Methods: We analyzed the association of STING with immune makers in TCGA datasets; we evaluated the efficacy of anti-PD-1 inhibitors by coculturing spleen cells with LLC cells in vitro, and inoculating wild type/STING knockdown LLC cells into the flank of wild-type/STING knockout mice in vivo. Furthermore, we measured the expression of STING by multiple immunohistochemistry and immunohistochemistry in lung cancer patients, and analyzed the relationship between expression level of STING in different cells and treatment efficacy of DCB(Durable clinical benefit : CR or PR or SD lasting longer than 6 months) and NDB(No durable clinical benefit : PD or SD that lasted ≤ 6 months) patients receiving immunotherapy. Results: Here we first demonstrated that STING signaling pathway activation was associated with better immunotherapy efficacy in lung cancer patients. Next, we identified two distinct STING expression pattern and found that STING in host cells not in tumor cells was positively correlated with infiltration of CD8+ T cells. More importantly, we demonstrated a loss of therapeutic efficacy of anti-PD-1 inhibitor in STING KO spleen cells and STING KO mice. In contrast, knock down of STING expression in tumor cells had no effect. Furthermore, expression of STING on host cells not in tumor cells was correlated with the efficacy of Anti-PD-1 inhibitors in lung cancer patients. Conclusion: Together, these findings demonstrate that STING expressed in host cells, rather than on tumor cells, plays an essential role in anti-PD-1 inhibitor therapy, suggesting that host intrinsic STING could be predictive of sensitivity to anti-PD-1 inhibitors. Citation Format: Li Zhou, Qiuli Xu, Litang Huang, Ping Zhan, mingxiang ye, Tangfeng Lv, Yong Song. Host intrinsic STING is a promising biomarkerfor predicting clinical efficacy of anti-PD-1 inhibitors in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1686.

Metabolic reprogramming and immune regulation in viral diseases.

The recent outbreak and transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide and the ensuing coronavirus disease 2019 (COVID-19) pandemic has left us scrambling for ways to contain the disease and develop vaccines that are safe and effective. Equally important, understanding the impact of the virus on the host system in convalescent patients, healthy otherwise or with co-morbidities, is expected to aid in developing effective strategies in the management of patients afflicted with the disease. Viruses possess the uncanny ability to redirect host metabolism to serve their needs and also limit host immune response to ensure their survival. An ever-increasingly powerful approach uses metabolomics to uncover diverse molecular signatures that influence a wide array of host signalling networks in different viral infections. This would also help integrate experimental findings from individual studies to yield robust evidence. In addition, unravelling the molecular mechanisms harnessed by both viruses and tumours in their host metabolism will help broaden the repertoire of therapeutic tools available to combat viral disease.

The Role of microRNAs and Long Non-Coding RNAs in the Regulation of the Immune Response to Mycobacterium tuberculosis Infection.

Non-coding RNAs have emerged as critical regulators of the immune response to infection. MicroRNAs (miRNAs) are small non-coding RNAs which regulate host defense mechanisms against viruses, bacteria and fungi. They are involved in the delicate interplay between Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and its host, which dictates the course of infection. Differential expression of miRNAs upon infection with M. tuberculosis, regulates host signaling pathways linked to inflammation, autophagy, apoptosis and polarization of macrophages. Experimental evidence suggests that virulent M. tuberculosis often utilize host miRNAs to promote pathogenicity by restricting host-mediated antibacterial signaling pathways. At the same time, host- induced miRNAs augment antibacterial processes such as autophagy, to limit bacterial proliferation. Targeting miRNAs is an emerging option for host-directed therapies. Recent studies have explored the role of long non-coding RNA (lncRNAs) in the regulation of the host response to mycobacterial infection. Among other functions, lncRNAs interact with chromatin remodelers to regulate gene expression and also function as miRNA sponges. In this review we attempt to summarize recent literature on how miRNAs and lncRNAs are differentially expressed during the course of M. tuberculosis infection, and how they influence the outcome of infection. We also discuss the potential use of non-coding RNAs as biomarkers of active and latent tuberculosis. Comprehensive understanding of the role of these non-coding RNAs is the first step towards developing RNA-based therapeutics and diagnostic tools for the treatment of TB.

Screening and identification of Theileria annulata subtelomere-encoded variable secreted protein-950454 (SVSP454) interacting proteins from bovine B cells

BackgroundTheileria annulata is a protozoan parasite that can infect and transform bovine B cells, macrophages, and dendritic cells. The mechanism of the transformation is still not well understood, and some parasite molecules have been identified, which contribute to cell proliferation by regulating host signaling pathways. Subtelomeric variable secreted proteins (SVSPs) of Theileria might affect the host cell phenotype, but its function is still not clear. Therefore, in the present study, we explored the interactions of SVSP454 with host cell proteins to investigate the molecular mechanism of T. annulata interaction with host cells.MethodsThe transcription level of an SVSP protein from T. annulata, SVSP454, was analyzed between different life stages and transformed cell passages using qRT-PCR. Then, SVSP454 was used as a bait to screen its interacting proteins from the bovine B cell cDNA library using a yeast two-hybrid (Y2H) system. The potential interacting proteins of host cells with SVSP454 were further identified by using a coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays.ResultsSVSP454 was transcribed in all three life stages of T. annulata but had the highest transcription during the schizont stage. However, the transcription level of SVSP454 continuously decreased as the cultures passaged. Two proteins, Bos Taurus coiled-coil domain 181 (CCDC181) and Bos Taurus mitochondrial ribosomal protein L30 (MRPL30), were screened. The proteins CCDC181 and MRPL30 of the host were further identified to directly interact with SVSP454.ConclusionIn the present study, SVSP454 was used as a bait plasmid, and its prey proteins CCDC181 and MRPL30 were screened out by using a Y2H system. Then, we demonstrated that SVSP454 directly interacted with both CCDC181 and MRPL30 by Co-IP and BiFC assays. Therefore, we speculate that SVSP454-CCDC181/SVSP454MRPL30 is an interacting axis that regulates the microtubule network and translation process of the host by some vital signaling molecules. Identification of the interaction of SVSP454 with CCDC181 and MRPL30 will help illustrate the transformation mechanisms induced by T. annulata.Graphic abstract

Short-Chain Fatty Acids as a Potential Treatment for Infections: a Closer Look at the Lungs.

Short-chain fatty acids (SCFAs) are the main metabolites produced by the gut microbiota via the fermentation of complex carbohydrates and fibers. Evidence suggests that SCFAs play a role in the control of infections through direct action both on microorganisms and on host signaling. This review summarizes the main microbicidal effects of SCFAs and discusses studies highlighting the effect of SCFAs in the virulence and viability of microorganisms. We also describe the diverse and complex modes of action of the SCFAs on the immune system in the face of infections with a specific focus on bacterial and viral respiratory infections. A growing body of evidence suggests that SCFAs protect against lung infections. Finally, we present potential strategies that may be leveraged to exploit the biological properties of SCFAs for increasing effectiveness and optimizing patient benefits.

Regulation of the Pseudomonas syringae Type III Secretion System by Host Environment Signals.

Pseudomonas syringae are Gram-negative, plant pathogenic bacteria that use a type III secretion system (T3SS) to disarm host immune responses and promote bacterial growth within plant tissues. Despite the critical role for type III secretion in promoting virulence, T3SS-encoding genes are not constitutively expressed by P. syringae and must instead be induced during infection. While it has been known for many years that culturing P. syringae in synthetic minimal media can induce the T3SS, relatively little is known about host signals that regulate the deployment of the T3SS during infection. The recent identification of specific plant-derived amino acids and organic acids that induce T3SS-inducing genes in P. syringae has provided new insights into host sensing mechanisms. This review summarizes current knowledge of the regulatory machinery governing T3SS deployment in P. syringae, including master regulators HrpRS and HrpL encoded within the T3SS pathogenicity island, and the environmental factors that modulate the abundance and/or activity of these key regulators. We highlight putative receptors and regulatory networks involved in linking the perception of host signals to the regulation of the core HrpRS–HrpL pathway. Positive and negative regulation of T3SS deployment is also discussed within the context of P. syringae infection, where contributions from distinct host signals and regulatory networks likely enable the fine-tuning of T3SS deployment within host tissues. Last, we propose future research directions necessary to construct a comprehensive model that (a) links the perception of host metabolite signals to T3SS deployment and (b) places these host–pathogen signaling events in the overall context of P. syringae infection.

Quercetin for COVID-19 and DENGUE co-infection: a potential therapeutic strategy of targeting critical host signal pathways triggered by SARS-CoV-2 and DENV.

BackgroundThe clinical consequences of SARS-CoV-2 and DENGUE virus co-infection are not promising. However, their treatment options are currently unavailable. Current studies have shown that quercetin is both resistant to COVID-19 and DENGUE; this study aimed to evaluate the possible functional roles and underlying mechanisms of action of quercetin as a potential molecular candidate against COVID-19 and DENGUE co-infection.MethodsWe used a series of bioinformatics analyses to understand and characterize the biological functions, pharmacological targets and therapeutic mechanisms of quercetin in COVID-19 and DENGUE co-infection.ResultsWe revealed the clinical characteristics of COVID-19 and DENGUE, including pathological mechanisms, key inflammatory pathways and possible methods of intervention, 60 overlapping targets related to the co-infection and the drug were identified, the protein–protein interaction (PPI) was constructed and TNFα, CCL-2 and CXCL8 could become potential drug targets. Furthermore, we disclosed the signaling pathways, biological functions and upstream pathway activity of quercetin in COVID-19 and DENGUE. The analysis indicated that quercetin could inhibit cytokines release, alleviate excessive immune responses and eliminate inflammation, through NF-κB, IL-17 and Toll-like receptor signaling pathway.ConclusionsThis study is the first to reveal quercetin as a pharmacological drug for COVID-19 and DENGUE co-infection. COVID-19 and DENGUE co-infection remain a potential threat to the world’s public health system. Therefore, we need innovative thinking to provide admissible evidence for quercetin as a potential molecule drug for the treatment of COVID-19 and DENGUE, but the findings have not been verified in actual patients, so further clinical drug trials are needed.

Open reading frame 3 protein of hepatitis E virus: Multi-function protein with endless potential.

Hepatitis E virus (HEV), a fecal-orally transmitted foodborne viral pathogen, causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the identification of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. HEV-open reading frame (ORF) 3, the smallest ORF in HEV genomes, initially had been perceived as an unremarkable HEV accessory protein. However, as novel HEV-ORF3 function has been discovered that is related to the existence of a putative third virion structural form, referred to as “quasi-enveloped” HEV particles, HEV is challenging the conventional virion structure-based classification scheme, which assigns all viruses to two groups, “enveloped” or “non-enveloped”. In this review, we systematically describe recent progress that has identified multiple pathogenic roles of HEV-ORF3, including roles in HEV virion release, biogenesis of quasi-enveloped virus, regulation of the host innate immune response, and interference with host signaling pathways. In addition, implications of HEV-ORF3-associated quasi-enveloped virions are discussed to guide future development of improved vaccines against zoonotic HEV infection.

Herbaspirillum seropedicae strain HRC54 expression profile in response to sugarcane apoplastic fluid.

The online version contains supplementary material available at 10.1007/s13205-021-02848-y.