cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13498978
title: gga-miR-1603 and gga-miR-1794 directly target viral L gene and function as a broad-spectrum antiviral factor against NDV replication

description: As the causative agent of Newcastle disease (ND), Newcastle disease virus (NDV) has seriously restricted the development of the poultry industry. Previous research has shown that miRNAs, members of the small noncoding RNA family, are implicated in the regulation NDV replication through extensive interactions with host mRNAs, but whether miRNAs affect NDV replication by directly binding to the NDV antigenome remains unclear. In this study, potential <i>Gallus gallus</i> miRNAs targeting the antigenome of NDV were bioinformatically predicted using the online software RegRNA 2.0, and gga-miR-1603 and gga-miR-1794 were identified as targeting the viral L gene directly through dual-luciferase reporter assays. Sequence alignment analysis demonstrated that multiple genotypes of NDVs harbored highly conserved binding sites for gga-miR-1603 and gga-miR-1794 in the viral antigenome located at 8611–8634 nt and 14,490–14,514 nt, respectively. Meanwhile, we found that gga-miR-1603 and gga-miR-1794 negatively regulated the expression of viral L gene at both the RNA and protein levels, as well as viral replication <i>in vitro</i>. Furthermore, NDV infection had no effect on endogenous gga-miR-1603 and gga-miR-1794 expression in various avian cell lines. Overall, our present study demonstrated that gga-miR-1603 and gga-miR-1794 directly bind to the viral L gene to facilitate ts degradation and inhibit the replication of multiple genotypes of NDVs <i>in vitro</i>. These findings will provide us with important clues for antiviral therapy against NDV infection.
DOI: 10.6084/m9.figshare.13498978.v1
title: gga-miR-1603 and gga-miR-1794 directly target viral L gene and function as a broad-spectrum antiviral factor against NDV replication

description: As the causative agent of Newcastle disease (ND), Newcastle disease virus (NDV) has seriously restricted the development of the poultry industry. Previous research has shown that miRNAs, members of the small noncoding RNA family, are implicated in the regulation NDV replication through extensive interactions with host mRNAs, but whether miRNAs affect NDV replication by directly binding to the NDV antigenome remains unclear. In this study, potential <i>Gallus gallus</i> miRNAs targeting the antigenome of NDV were bioinformatically predicted using the online software RegRNA 2.0, and gga-miR-1603 and gga-miR-1794 were identified as targeting the viral L gene directly through dual-luciferase reporter assays. Sequence alignment analysis demonstrated that multiple genotypes of NDVs harbored highly conserved binding sites for gga-miR-1603 and gga-miR-1794 in the viral antigenome located at 8611–8634 nt and 14,490–14,514 nt, respectively. Meanwhile, we found that gga-miR-1603 and gga-miR-1794 negatively regulated the expression of viral L gene at both the RNA and protein levels, as well as viral replication <i>in vitro</i>. Furthermore, NDV infection had no effect on endogenous gga-miR-1603 and gga-miR-1794 expression in various avian cell lines. Overall, our present study demonstrated that gga-miR-1603 and gga-miR-1794 directly bind to the viral L gene to facilitate ts degradation and inhibit the replication of multiple genotypes of NDVs <i>in vitro</i>. These findings will provide us with important clues for antiviral therapy against NDV infection.
DOI: 10.6084/m9.figshare.14916624.v1
title: Profiling the immune response to <i>Mycobacterium tuberculosis</i> Beijing family infection: a perspective from the transcriptome

description: Tuberculosis continues to be an important public health problem. Particularly considering Beijing-family strains of <i>Mycobacterium tuberculosis</i>, which have been associated with drug-resistance and hypervirulence. The Beijing-like SIT190 (BL) is the most prevalent Beijing strain in Colombia. The pathogenic mechanism and immune response against this pathogen is unknown. Thus, we compared the course of pulmonary TB in BALB/c mice infected with Classical-Beijing strain 391 and BL strain 323. The disease course was different among infected animals with Classical-Beijing and BL strain. Mice infected with BL had a 100% mortality at 45 days post-infection (dpi), with high bacillary loads and massive pneumonia, whereas infected animals with Classical-Beijing survived until 60 dpi and showed extensive pneumonia and necrosis. Lung RNA extraction was carried out at early (day 3 dpi), intermediate (day 14 dpi), and late (days 28 and 60 dpi) time points of infection. Transcriptional analysis of infected mice with Classical-Beijing showed several over-expressed genes, associated with a pro-inflammatory profile, including those for coding for CCL3 and CCL4 chemokines, both biomarkers of disease severity. Conversely, mice infected with BL displayed a profile which included the over-expression of several genes associated with immune-suppression, including <i>Nkiras, Dleu2,</i> and <i>Sphk2</i>, highlighting an anti-inflammatory milieu which would allow high bacterial replication followed by an intense inflammatory response. In summary, both Beijing strains induced a non-protective immune response which induced extensive tissue damage, BL strain induced rapidly extensive pneumonia and death, whereas Classical-Beijing strain produced slower extensive pneumonia later associated with extensive necrosis.
DOI: 10.6084/m9.figshare.16586946
title: The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

description: An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species (mito-ROS) and CD147, a host protein that mediates viral entry. 4 F also reduced associated cellular apoptosis and secretion of IL-6 in both SARS-CoV-2 infected Vero-E6 and Calu3 cells. Thus, 4 F attenuates <i>in vitro</i> SARS-CoV-2 replication, associated apoptosis in epithelial cells and secretion of IL-6, a major cytokine related to COVID-19 morbidity. Given established safety of 4 F in humans, clinical studies are warranted to establish 4 F as therapy for COVID-19.
DOI: 10.6084/m9.figshare.14866869
title: Adaptation of the emerging pathogenic yeast <i>Candida auris</i> to high caspofungin concentrations correlates with cell wall changes

description: <i>Candida auris</i> has emerged as a fungal pathogen that causes nosocomial outbreaks worldwide. Diseases caused by this fungus are of concern, due to its reduced susceptibility to several antifungals. <i>C. auris</i> exhibits paradoxical growth (PG; defined as growth at high, but not intermediate antifungal concentrations) in the presence of caspofungin (CPF). We have characterized the cellular changes associated with adaptation to CPF. Using EUCAST AFST protocols, all <i>C. auris</i> isolates tested showed PG to CPF, although in some isolates it was more prominent. Most isolates also showed a trailing effect (TE) to micafungin and anidulafungin. We identified two <i>FKS</i> genes in <i>C. auris</i> that encode the echinocandins target, namely β-1,3-glucan synthase. <i>FKS1</i> contained the consensus hot-spot (HS) 1 and HS2 sequences. <i>FKS2</i> only contained the HS1 region which had a change (F635Y), that has been shown to confer resistance to echinocandins in <i>C. glabrata</i>. PG has been characterized in other species, mainly <i>C. albicans</i>, where high CPF concentrations induced an increase in chitin, cell volume and aggregation. In <i>C. auris</i> CPF only induced a slight accumulation of chitin, and none of the other phenomena. RNAseq experiments demonstrated that CPF induced the expression of genes encoding several GPI-anchored cell wall proteins, membrane proteins required for the stability of the cell wall, chitin synthase and mitogen-activated protein kinases (MAPKs) involved in cell integrity, such as <i>BCK2, HOG1</i> and <i>MKC1</i> (<i>SLT2</i>). Our work highlights some of the processes induced in <i>C. auris</i> to adapt to echinocandins.
DOI: 10.6084/m9.figshare.14866869.v3
title: Adaptation of the emerging pathogenic yeast <i>Candida auris</i> to high caspofungin concentrations correlates with cell wall changes

description: <i>Candida auris</i> has emerged as a fungal pathogen that causes nosocomial outbreaks worldwide. Diseases caused by this fungus are of concern, due to its reduced susceptibility to several antifungals. <i>C. auris</i> exhibits paradoxical growth (PG; defined as growth at high, but not intermediate antifungal concentrations) in the presence of caspofungin (CPF). We have characterized the cellular changes associated with adaptation to CPF. Using EUCAST AFST protocols, all <i>C. auris</i> isolates tested showed PG to CPF, although in some isolates it was more prominent. Most isolates also showed a trailing effect (TE) to micafungin and anidulafungin. We identified two <i>FKS</i> genes in <i>C. auris</i> that encode the echinocandins target, namely β-1,3-glucan synthase. <i>FKS1</i> contained the consensus hot-spot (HS) 1 and HS2 sequences. <i>FKS2</i> only contained the HS1 region which had a change (F635Y), that has been shown to confer resistance to echinocandins in <i>C. glabrata</i>. PG has been characterized in other species, mainly <i>C. albicans</i>, where high CPF concentrations induced an increase in chitin, cell volume and aggregation. In <i>C. auris</i> CPF only induced a slight accumulation of chitin, and none of the other phenomena. RNAseq experiments demonstrated that CPF induced the expression of genes encoding several GPI-anchored cell wall proteins, membrane proteins required for the stability of the cell wall, chitin synthase and mitogen-activated protein kinases (MAPKs) involved in cell integrity, such as <i>BCK2, HOG1</i> and <i>MKC1</i> (<i>SLT2</i>). Our work highlights some of the processes induced in <i>C. auris</i> to adapt to echinocandins.
DOI: 10.6084/m9.figshare.14866869.v4
title: Adaptation of the emerging pathogenic yeast <i>Candida auris</i> to high caspofungin concentrations correlates with cell wall changes

description: <i>Candida auris</i> has emerged as a fungal pathogen that causes nosocomial outbreaks worldwide. Diseases caused by this fungus are of concern, due to its reduced susceptibility to several antifungals. <i>C. auris</i> exhibits paradoxical growth (PG; defined as growth at high, but not intermediate antifungal concentrations) in the presence of caspofungin (CPF). We have characterized the cellular changes associated with adaptation to CPF. Using EUCAST AFST protocols, all <i>C. auris</i> isolates tested showed PG to CPF, although in some isolates it was more prominent. Most isolates also showed a trailing effect (TE) to micafungin and anidulafungin. We identified two <i>FKS</i> genes in <i>C. auris</i> that encode the echinocandins target, namely β-1,3-glucan synthase. <i>FKS1</i> contained the consensus hot-spot (HS) 1 and HS2 sequences. <i>FKS2</i> only contained the HS1 region which had a change (F635Y), that has been shown to confer resistance to echinocandins in <i>C. glabrata</i>. PG has been characterized in other species, mainly <i>C. albicans</i>, where high CPF concentrations induced an increase in chitin, cell volume and aggregation. In <i>C. auris</i> CPF only induced a slight accumulation of chitin, and none of the other phenomena. RNAseq experiments demonstrated that CPF induced the expression of genes encoding several GPI-anchored cell wall proteins, membrane proteins required for the stability of the cell wall, chitin synthase and mitogen-activated protein kinases (MAPKs) involved in cell integrity, such as <i>BCK2, HOG1</i> and <i>MKC1</i> (<i>SLT2</i>). Our work highlights some of the processes induced in <i>C. auris</i> to adapt to echinocandins.
DOI: 10.6084/m9.figshare.16877124
title: Sweeping analysis of transcript profile in dengue virus serotype 3 infection and antibody-dependent enhancement of infection

description: Dengue virus infection mainly causes dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). However, ADE (antibody-dependent enhancement) is one of the main pathogenic factors, and its pathogenic mechanism has not been fully elucidated. Recently, with the development of high-throughput sequencing, an increased number of RNAs have been confirmed to play a vital regulatory role in the process of virus infection. However, there is a lack of research on dengue virus infection and ADE. In this study, we used RNA-Seq to detect differentially expressed RNAs (DE RNAs) profiles in mock-infected, DENV-3-infected, and ADE-infected THP-1 cells. Firstly, we found 69 circRNAs, 259 miRNAs, and 18 mRNAs were differentially expressed in THP-1 vs DENV-3. In THP-1 vs ADE, 94 circRNAs, 263 miRNAs, and 111 mRNAs were differentially expressed. In DENV-3 vs ADE, 68 circRNAs, 105 miRNAs, and 94 mRNAs were differentially expressed. Functional enrichment analysis of these DE RNAs mainly focused on immune system, viral infectious diseases, cytokine-cytokine receptor interactions, and NOD/RIG-I-like receptor signaling pathways. In DENV-3 vs ADE, notably, the expression of HBB was up-regulated, which was a Fcγ Receptor-mediated phagocytosis protein. Additionally, we predicted the encoding ability of DE circRNAs, and it was found that a small peptide was encoded by novel_circ_001562 and that its amino acid sequence was consistent with that of DDX60L, which is a class of interferon-stimulated genes. Finally, we constructed the ceRNA regulatory network pathway. Therefore, our study provides a new strategy for further investigation on DENV-host interactions.
DOI: 10.6084/m9.figshare.16877124.v1
title: Sweeping analysis of transcript profile in Dengue virus serotype 3 infection and Antibody-Dependent Enhancement of Infection

description: Dengue virus infection mainly causes dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). However, ADE (antibody-dependent enhancement) is one of the main pathogenic factors, and its pathogenic mechanism has not been fully elucidated. Recently, with the development of high-throughput sequencing, an increased number of RNAs have been confirmed to play a vital regulatory role in the process of virus infection. However, there is a lack of research on dengue virus infection and ADE. In this study, we used RNA-Seq to detect differentially expressed RNAs (DE RNAs) profiles in mock-infected, DENV-3-infected, and ADE-infected THP-1 cells. Firstly, we found 69 circRNAs, 259 miRNAs, and 18 mRNAs were differentially expressed in THP-1 vs DENV-3. In THP-1 vs ADE, 94 circRNAs, 263 miRNAs, and 111 mRNAs were differentially expressed. In DENV-3 vs ADE, 68 circRNAs, 105 miRNAs, and 94 mRNAs were differentially expressed. Functional enrichment analysis of these DE RNAs mainly focused on immune system, viral infectious diseases, cytokine-cytokine receptor interactions, and NOD/RIG-I-like receptor signalling pathways. In DENV-3 vs ADE, notably, the expression of HBB was up-regulated, which was a Fcγ Receptor-mediated phagocytosis protein. Additionally, we predicted the encoding ability of DE circRNAs, and it was found that a small peptide was encoded by novel_circ_001562 and that its amino acid sequence was consistent with that of DDX60L, which is a class of interferon-stimulated genes. Finally, we constructed the ceRNA regulatory network pathway. Therefore, our study provides a new strategy for further investigation on DENV-host interactions.
DOI: 10.6084/m9.figshare.16877124.v2
title: Sweeping analysis of transcript profile in dengue virus serotype 3 infection and antibody-dependent enhancement of infection

description: Dengue virus infection mainly causes dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). However, ADE (antibody-dependent enhancement) is one of the main pathogenic factors, and its pathogenic mechanism has not been fully elucidated. Recently, with the development of high-throughput sequencing, an increased number of RNAs have been confirmed to play a vital regulatory role in the process of virus infection. However, there is a lack of research on dengue virus infection and ADE. In this study, we used RNA-Seq to detect differentially expressed RNAs (DE RNAs) profiles in mock-infected, DENV-3-infected, and ADE-infected THP-1 cells. Firstly, we found 69 circRNAs, 259 miRNAs, and 18 mRNAs were differentially expressed in THP-1 vs DENV-3. In THP-1 vs ADE, 94 circRNAs, 263 miRNAs, and 111 mRNAs were differentially expressed. In DENV-3 vs ADE, 68 circRNAs, 105 miRNAs, and 94 mRNAs were differentially expressed. Functional enrichment analysis of these DE RNAs mainly focused on immune system, viral infectious diseases, cytokine-cytokine receptor interactions, and NOD/RIG-I-like receptor signaling pathways. In DENV-3 vs ADE, notably, the expression of HBB was up-regulated, which was a Fcγ Receptor-mediated phagocytosis protein. Additionally, we predicted the encoding ability of DE circRNAs, and it was found that a small peptide was encoded by novel_circ_001562 and that its amino acid sequence was consistent with that of DDX60L, which is a class of interferon-stimulated genes. Finally, we constructed the ceRNA regulatory network pathway. Therefore, our study provides a new strategy for further investigation on DENV-host interactions.
DOI: 10.6084/m9.figshare.14333024
title: Altered expression of genes related to innate antifungal immunity in the absence of galectin-3

description: Galectin-3 (Gal-3) is the most studied member of the animal galectin family, which comprises β-galactoside-binding lectins and participates in several cellular events. Its expression in cells involved in innate and adaptive immunity is related to anti- and proinflammatory functions, signaling an important role in inflammatory, infectious, and tumorigenesis processes. Mice deficient in Gal-3 exhibit important phenotypes, but it is unclear whether these phenotypes reflect an impairment of the functions of this protein. Gal-3 plays an important role in modulating the immune response to different pathogenic microorganisms. However, the role of Gal-3 in immunity to infection is still poorly understood. Therefore, we investigated the effects of Gal-3 deletion on the expression of genes involved in the innate immune response in the lungs, spleens, and brains of Gal-3 KO mice. Gene profiling expression analysis suggested that Gal-3 deletion resulted in differentially modulated expression of the genes encoding beta-glucan, mannose and chitin-responsive pattern recognition receptors, signal transduction, inflammation, and phagocytosis. Our data thus suggest the importance of Gal-3 expression in the host innate immune system.
DOI: 10.6084/m9.figshare.14333024.v1
title: Altered expression of genes related to innate antifungal immunity in the absence of galectin-3

description: Galectin-3 (Gal-3) is the most studied member of the animal galectin family, which comprises β-galactoside-binding lectins and participates in several cellular events. Its expression in cells involved in innate and adaptive immunity is related to anti- and proinflammatory functions, signaling an important role in inflammatory, infectious, and tumorigenesis processes. Mice deficient in Gal-3 exhibit important phenotypes, but it is unclear whether these phenotypes reflect an impairment of the functions of this protein. Gal-3 plays an important role in modulating the immune response to different pathogenic microorganisms. However, the role of Gal-3 in immunity to infection is still poorly understood. Therefore, we investigated the effects of Gal-3 deletion on the expression of genes involved in the innate immune response in the lungs, spleens, and brains of Gal-3 KO mice. Gene profiling expression analysis suggested that Gal-3 deletion resulted in differentially modulated expression of the genes encoding beta-glucan, mannose and chitin-responsive pattern recognition receptors, signal transduction, inflammation, and phagocytosis. Our data thus suggest the importance of Gal-3 expression in the host innate immune system.
DOI: 10.6084/m9.figshare.14278016
title: Immune dysregulation and system pathology in COVID-19

description: The coronavirus disease 19 (COVID-19) caused by the novel coronavirus known as SARS-CoV-2 has caused a global public health crisis. As of 7 January 2021, 87,640,402 confirmed cases and 1,891,692 mortalities have been reported worldwide. Studies focusing on the epidemiological and clinical characteristics of COVID-19 patients have suggested a dysregulated immune response characterized by lymphopenia and cytokine storm in these patients. The exaggerated immune response induced by the cytokine storm causes septic shock, acute respiratory distress syndrome (ARDS), and/or multiple organs failure, which increases the fatality rate of patients with SARS-CoV-2 infection. Herein, we review the recent research progress on epidemiology, clinical features, and system pathology in COVID-19. Moreover, we summarized the recent therapeutic strategies, which are either approved, under clinical trial, and/or under investigation by the local or global health authorities. We assume that treatments should focus on the use of antiviral drugs in combination with immunomodulators as well as treatment of the underlying comorbidities.
DOI: 10.6084/m9.figshare.14278016.v1
title: Immune dysregulation and system pathology in COVID-19

description: The coronavirus disease 19 (COVID-19) caused by the novel coronavirus known as SARS-CoV-2 has caused a global public health crisis. As of 7 January 2021, 87,640,402 confirmed cases and 1,891,692 mortalities have been reported worldwide. Studies focusing on the epidemiological and clinical characteristics of COVID-19 patients have suggested a dysregulated immune response characterized by lymphopenia and cytokine storm in these patients. The exaggerated immune response induced by the cytokine storm causes septic shock, acute respiratory distress syndrome (ARDS), and/or multiple organs failure, which increases the fatality rate of patients with SARS-CoV-2 infection. Herein, we review the recent research progress on epidemiology, clinical features, and system pathology in COVID-19. Moreover, we summarized the recent therapeutic strategies, which are either approved, under clinical trial, and/or under investigation by the local or global health authorities. We assume that treatments should focus on the use of antiviral drugs in combination with immunomodulators as well as treatment of the underlying comorbidities.
DOI: 10.6084/m9.figshare.16611534.v2
title: A clubroot pathogen effector targets cruciferous cysteine proteases to suppress plant immunity

description: Plant pathogen effector proteins are key to pathogen virulence. In susceptible host Brassicas, the clubroot pathogen, <i>Plasmodiophora brassicae</i>, induces the production of nutrient-sink root galls, at the site of infection. Among a list of 32 <i>P. brassiae</i> effector candidates previously reported by our group, we identified SSPbP53 as a putative apoplastic cystatin-like protein highly expressed during the secondary infection. Here we found that SSPbP53 encoding gene is conserved among several <i>P. brassicae</i> pathotypes and that SSPbP53 is an apoplastic protein able to directly interact with and inhibit cruciferous papain-like cysteine proteases (PLCPs), specifically Arabidopsis XYLEM CYSTEINE PEPTIDASE 1 (<i>At</i>XCP1). The severity of clubroot disease is greatly reduced in the Arabidopsis <i>xcp1</i> null mutant (<i>At</i>Δ<i>xcp1</i>) after infection with <i>P. brassicae</i> resting spores, indicating that the interaction of <i>P. brassicae</i> SSPbP53 with XCP1 is important to clubroot susceptibility. SSPbP53 is the first cystatin-like effector identified and characterized for a plant pathogenic protist.