cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30764565.v1
title: Chronic viral infections impaired the growth process of splenic B cells by upregulating Bbc3 and Atf3 in LCMV-CL13 infected mouse model

description: Chronic persistent viral infections can lead to significant spleen damage, thus disrupting the host humoral immune response; however, the underlying mechanisms remain unclear. In this study, we employed a Lymphocytic choriomeningitis virus (LCMV) chronic infection model to investigate the effects of virus infection on spleen damage. Mice infected with Lymphocytic choriomeningitis virus clone 13 (LCMV-CL13) presented a series of pathological features, such as white pulp atrophy and reduced germinal center diameter, length, and area in the spleen. More importantly, we observed a diminished GC response alongside a weak antibody response in the chronic infection model. Single-cell RNA sequencing (scRNA-seq) further revealed the dysregulation of gene expression, including <i>Bbc3</i>, <i>Atf3</i>, and <i>Ptpn6</i>, which inhibit B-cell differentiation during chronic viral infection. We verify that the upregulation of <i>Bbc3</i> or <i>Atf3</i>, respectively, can promote apoptosis in BaF3 cells. Immune repertoire (IR) analysis revealed that the molecular diversity of the BCR repertoire after LCMV-CL13 infection, specifically manifested in BCR clonal diversity, <i>IGHV</i> gene segment usage preference, and CDR3 sequence changes. In conclusion, this study demonstrated that chronic LCMV-CL13 infection interrupted the development of splenic B cells by increasing the expression of apoptosis genes, thus enhancing our understanding of the underlying mechanisms of B-cell development interruption during chronic viral infection.
DOI: 10.6084/m9.figshare.30021882
title: Preliminary assessment of the therapeutic potential of staphylococcal enterotoxin-like W via biological activity and TCR binding sites analysis

description: Staphylococcal enterotoxin-like W (SElW) is a novel, widely prevalent enterotoxin-like protein that functions as a classical staphylococcal superantigen (SAg) and has been shown to exacerbate infections caused by the <i>S. aureus</i> epidemic clone CC398. However, the genetic distribution and amino acid polymorphisms, biological and antitumor activity, and T cell receptor (TCR) binding sites of SElW in <i>S. aureus</i> strains prevalent in China have not been investigated. The carrier rate and distribution of <i>selw</i> were determined by PCR, the stability and antitumor activity of recombinant SElW (rSElW) protein were evaluated. The superantigen activity of the five mutants (Y18A, N19A, W55A, C88A, and C98A) was compared to that of wild-type SElW (WT-rSElW) to assess the role of these sites in mediating TCR binding. The <i>selw</i> gene was detected in all (986/986, 100%) dominant clonal lineages of <i>S. aureus</i> and most strains (69.1%, 56/81) had a full-length <i>selw</i> open reading frame with a sequence identity of 90.5%. rSElW was heat-stable but not resistant to pepsin and trypsin digestion. Additionally, rSElW significantly inhibited the proliferation of MCF-7 and AGS, but not A549 <i>in vitro</i>. The rSElW mutants C88A and C98A markedly reduced T cell proliferation and IL-2, IFN-γ and TNF-α secretion compared to WT-rSElW. rSElW is a highly prevalent SAg that binds to the TCR via C98 and C88, which may serve as novel therapeutic targets for <i>S. aureus</i> infections and its application in anti-tumor activity needs to be further evaluated <i>in vivo.</i>
DOI: 10.6084/m9.figshare.30021882.v1
title: Preliminary assessment of the therapeutic potential of staphylococcal enterotoxin-like W via biological activity and TCR binding sites analysis

description: Staphylococcal enterotoxin-like W (SElW) is a novel, widely prevalent enterotoxin-like protein that functions as a classical staphylococcal superantigen (SAg) and has been shown to exacerbate infections caused by the <i>S. aureus</i> epidemic clone CC398. However, the genetic distribution and amino acid polymorphisms, biological and antitumor activity, and T cell receptor (TCR) binding sites of SElW in <i>S. aureus</i> strains prevalent in China have not been investigated. The carrier rate and distribution of <i>selw</i> were determined by PCR, the stability and antitumor activity of recombinant SElW (rSElW) protein were evaluated. The superantigen activity of the five mutants (Y18A, N19A, W55A, C88A, and C98A) was compared to that of wild-type SElW (WT-rSElW) to assess the role of these sites in mediating TCR binding. The <i>selw</i> gene was detected in all (986/986, 100%) dominant clonal lineages of <i>S. aureus</i> and most strains (69.1%, 56/81) had a full-length <i>selw</i> open reading frame with a sequence identity of 90.5%. rSElW was heat-stable but not resistant to pepsin and trypsin digestion. Additionally, rSElW significantly inhibited the proliferation of MCF-7 and AGS, but not A549 <i>in vitro</i>. The rSElW mutants C88A and C98A markedly reduced T cell proliferation and IL-2, IFN-γ and TNF-α secretion compared to WT-rSElW. rSElW is a highly prevalent SAg that binds to the TCR via C98 and C88, which may serve as novel therapeutic targets for <i>S. aureus</i> infections and its application in anti-tumor activity needs to be further evaluated <i>in vivo.</i>
DOI: 10.6084/m9.figshare.29108489
title: Glycogen synthase kinase 3 promotes the proliferation of porcine epidemic diarrhoea virus by phosphorylating the nucleocapsid protein

description: Porcine epidemic diarrhoea virus (PEDV) is a highly pathogenic porcine enteric coronavirus that causes severe watery diarrhoea and mortality in piglets. The nucleocapsid protein (N) is the most abundant viral protein and is highly phosphorylated, with the phosphorylation level directly affecting infection and proliferation. Here, we characterized the phosphorylation level of the N protein and found that its SR (Ser and Arg) motif was highly phosphorylated. The phosphorylation level significantly decreased after mutation of threonine (Thr) to serine (Ser). Through screening, it was determined that GSK3α/β plays a major role in phosphorylating the SR motif. Using GSK3α/β inhibitors or directly knocking out the GSK3α/β gene significantly inhibit PEDV proliferation. Finally, we used yeast recombination technology to develop a reverse genetics system for assessing PEDV and confirmed that no differences existed between the wild-type strain and the rescued virus. Using this platform, we generated a PEDV N protein SR motif mutant strain. We found that, compared to the wild-type strain, the proliferation of the mutant strain was significantly weakened, confirming that the phosphorylation of the SR motif is crucial for PEDV proliferation. In summary, we verified the phosphorylation sites of the PEDV N protein and the associated protein kinases, providing new insights into the development of relevant therapeutic strategies.
DOI: 10.6084/m9.figshare.29108489.v1
title: Glycogen synthase kinase 3 promotes the proliferation of porcine epidemic diarrhoea virus by phosphorylating the nucleocapsid protein

description: Porcine epidemic diarrhoea virus (PEDV) is a highly pathogenic porcine enteric coronavirus that causes severe watery diarrhoea and mortality in piglets. The nucleocapsid protein (N) is the most abundant viral protein and is highly phosphorylated, with the phosphorylation level directly affecting infection and proliferation. Here, we characterized the phosphorylation level of the N protein and found that its SR (Ser and Arg) motif was highly phosphorylated. The phosphorylation level significantly decreased after mutation of threonine (Thr) to serine (Ser). Through screening, it was determined that GSK3α/β plays a major role in phosphorylating the SR motif. Using GSK3α/β inhibitors or directly knocking out the GSK3α/β gene significantly inhibit PEDV proliferation. Finally, we used yeast recombination technology to develop a reverse genetics system for assessing PEDV and confirmed that no differences existed between the wild-type strain and the rescued virus. Using this platform, we generated a PEDV N protein SR motif mutant strain. We found that, compared to the wild-type strain, the proliferation of the mutant strain was significantly weakened, confirming that the phosphorylation of the SR motif is crucial for PEDV proliferation. In summary, we verified the phosphorylation sites of the PEDV N protein and the associated protein kinases, providing new insights into the development of relevant therapeutic strategies.
DOI: 10.6084/m9.figshare.28418166
title: Short-term antiretroviral therapy may not correct the dysregulations of plasma virome and cytokines induced by HIV-1 infection

description: An expansion of plasma anelloviruses and dysregulation of inflammation was associated with HIV-1 infection. However, how antiretroviral therapy (ART) affects the dynamics of plasma virome and cytokine profile remains largely unknown. To characterize the dynamics of plasma virome and cytokines in HIV-1-infected individuals before and during the first year of ART, a cohort of 26 HIV-1-infected individuals and 19 healthy controls was recruited. Blood samples were collected and subjected to metagenomic analysis and the measurement of 27 cytokines. Metagenomic analysis revealed an increased abundance and prevalence of human pegivirus type 1 (HPgV-1) and a slightly decreased diversity and abundance of anellovirus in plasma of HIV-1-infected individuals after ART. No obvious impact was observed on other plasma commensal viruses. Increased abundance and prevalence of HPgV-1 were further confirmed by RT-qPCR assay in a larger cohort of 114 HIV-1-infected individuals. Notably, most dysregulated cytokines were not fully restored by ART, with extremely abnormal levels of IL-10, GM-CSF, VEGF, and eotaxin, and a significantly increased level of plasma I-FABP. Anelloviruses showed significantly negative correlations with other commensal viruses except HPgV-1 but had positive correlations with several anti-inflammatory and Th1 cytokines. These results suggest that short-term ART may not significantly correct the virome and cytokine dysregulations induced by HIV-1 infection. The results highlight a need for further investigation into the long-term effects of ART on virome and cytokine profiles in HIV-1-infected individuals.
DOI: 10.6084/m9.figshare.28418166.v1
title: Short-term antiretroviral therapy may not correct the dysregulations of plasma virome and cytokines induced by HIV-1 infection

description: An expansion of plasma anelloviruses and dysregulation of inflammation was associated with HIV-1 infection. However, how antiretroviral therapy (ART) affects the dynamics of plasma virome and cytokine profile remains largely unknown. To characterize the dynamics of plasma virome and cytokines in HIV-1-infected individuals before and during the first year of ART, a cohort of 26 HIV-1-infected individuals and 19 healthy controls was recruited. Blood samples were collected and subjected to metagenomic analysis and the measurement of 27 cytokines. Metagenomic analysis revealed an increased abundance and prevalence of human pegivirus type 1 (HPgV-1) and a slightly decreased diversity and abundance of anellovirus in plasma of HIV-1-infected individuals after ART. No obvious impact was observed on other plasma commensal viruses. Increased abundance and prevalence of HPgV-1 were further confirmed by RT-qPCR assay in a larger cohort of 114 HIV-1-infected individuals. Notably, most dysregulated cytokines were not fully restored by ART, with extremely abnormal levels of IL-10, GM-CSF, VEGF, and eotaxin, and a significantly increased level of plasma I-FABP. Anelloviruses showed significantly negative correlations with other commensal viruses except HPgV-1 but had positive correlations with several anti-inflammatory and Th1 cytokines. These results suggest that short-term ART may not significantly correct the virome and cytokine dysregulations induced by HIV-1 infection. The results highlight a need for further investigation into the long-term effects of ART on virome and cytokine profiles in HIV-1-infected individuals.
DOI: 10.6084/m9.figshare.29856127
title: Exogenous proline promotes serum killing of <i>Klebsiella pneumoniae</i>

description: <i>Klebsiella pneumoniae</i>, a common pathogen responsible for bloodstream infections, can evade clearance by the complement-dependent killing in serum, known as serum resistance. However, strategy in managing <i>K. pneumoniae</i> serum resistance is still lacking. In this study, we employed metabolomics to identify the metabolic features of <i>K. pneumoniae</i>. We found that the pyruvate/TCA cycle and alanine, aspartate, and glutamate metabolic pathways were significantly downregulated. Proline, identified as a key biomarker, effectively increased the serum sensitivity to multiple <i>K. pneumoniae</i> clinical isolates and restored the bactericidal activity of complement. The <i>in vivo</i> synergistic effect of proline was validated in a murine infection model. Furthermore, we demonstrated that proline activates the pyruvate/TCA cycle, increases proton motive force, and enhances complement proteins binding to bacterial surface, forming membrane attack complex to kill serum-resistant <i>K. pneumoniae</i>. Our findings provide new insights for the development of metabolism-based approach to manage <i>K. pneumoniae</i> serum resistance and offer potential targets and strategies for host immunity-based anti-infection therapies.
DOI: 10.6084/m9.figshare.29856127.v2
title: Exogenous proline promotes serum killing of <i>Klebsiella pneumoniae</i>

description: <i>Klebsiella pneumoniae</i>, a common pathogen responsible for bloodstream infections, can evade clearance by the complement-dependent killing in serum, known as serum resistance. However, strategy in managing <i>K. pneumoniae</i> serum resistance is still lacking. In this study, we employed metabolomics to identify the metabolic features of <i>K. pneumoniae</i>. We found that the pyruvate/TCA cycle and alanine, aspartate, and glutamate metabolic pathways were significantly downregulated. Proline, identified as a key biomarker, effectively increased the serum sensitivity to multiple <i>K. pneumoniae</i> clinical isolates and restored the bactericidal activity of complement. The <i>in vivo</i> synergistic effect of proline was validated in a murine infection model. Furthermore, we demonstrated that proline activates the pyruvate/TCA cycle, increases proton motive force, and enhances complement proteins binding to bacterial surface, forming membrane attack complex to kill serum-resistant <i>K. pneumoniae</i>. Our findings provide new insights for the development of metabolism-based approach to manage <i>K. pneumoniae</i> serum resistance and offer potential targets and strategies for host immunity-based anti-infection therapies.
DOI: 10.6084/m9.figshare.29856127.v1
title: Exogenous proline promotes serum killing of <i>klebsiella pneumoniae</i>

description: <i>Klebsiella pneumoniae</i>, a common pathogen responsible for bloodstream infections, can evade clearance by the complement-dependent killing in serum, known as serum resistance. However, strategy in managing <i>K. pneumoniae</i> serum resistance is still lacking. In this study, we employed metabolomics to identify the metabolic features of <i>K. pneumoniae</i>. We found that the pyruvate/TCA cycle and alanine, aspartate, and glutamate metabolic pathways were significantly downregulated. Proline, identified as a key biomarker, effectively increased the serum sensitivity to multiple <i>K. pneumoniae</i> clinical isolates and restored the bactericidal activity of complement. The <i>in vivo</i> synergistic effect of proline was validated in a murine infection model. Furthermore, we demonstrated that proline activates the pyruvate/TCA cycle, increase proton motive force and enhance complement proteins binding to bacterial surface, forming membrane attack complex to kill serum-resistant <i>K. pneumoniae</i>. Our findings provide new insights for the development of metabolism-based approach to manage <i>K. pneumoniae</i> serum resistance and offer potential targets and strategies for host immunity-based anti-infection therapies.
DOI: 10.6084/m9.figshare.29957085
title: Phage pAEv1: A potential biocontrol agent against <i>Aeromonas veronii</i> infections

description: <i>Aeromonas veronii</i>, a significant aquaculture pathogen, induces substantial mortality in farmed aquatic species. Given the therapeutic promise of phage-mediated bacterial lysis, we isolated <i>A. veronii</i> from contaminated aquaculture systems and characterized its biological properties. Concurrently, the phage pAEv1 was recovered from the same aquatic environment using the pathogen as a host. Biological characterization revealed an optimal multiplicity of infection (MOI) of 0.01, a 10-min latent period, and a titer of 1.3 × 10<sup>8</sup> PFU/mL. pAEv1 exhibited notable stability, maintaining infectivity at temperatures ranging from −80°C to 55°C and pH levels of 5–9. Genomic analysis identified a circular double-stranded DNA genome, closely related to the <i>Aeromonas</i> phage pAEv1812 (ID: OL964754.1), with UniProtKB-based functional annotation categorizing encoded proteins into DNA modification and structural classes. COG and KEGG analyses further demonstrated gene enrichment in nucleic acid metabolism and purine biosynthesis, consistent with phage replication machinery. Crucially, virulence factor screening confirmed the absence of resistance or virulence genes, ensuring genetic-level biosafety. <i>In vitro</i> antimicrobial tests showed that phage pAEv1 effectively inhibited <i>A. veronii</i>. Additionally, <i>in vivo</i> experiments demonstrated that grass carp treated with pAEv1 had an 80% survival rate after 7 days of exposure to a double minimum lethal dose (MLD) of the bacterium.
DOI: 10.6084/m9.figshare.29957085.v1
title: Phage pAEv1: A potential biocontrol agent against <i>Aeromonas veronii</i> infections

description: <i>Aeromonas veronii</i>, a significant aquaculture pathogen, induces substantial mortality in farmed aquatic species. Given the therapeutic promise of phage-mediated bacterial lysis, we isolated <i>A. veronii</i> from contaminated aquaculture systems and characterized its biological properties. Concurrently, the phage pAEv1 was recovered from the same aquatic environment using the pathogen as a host. Biological characterization revealed an optimal multiplicity of infection (MOI) of 0.01, a 10-min latent period, and a titer of 1.3 × 10<sup>8</sup> PFU/mL. pAEv1 exhibited notable stability, maintaining infectivity at temperatures ranging from −80°C to 55°C and pH levels of 5–9. Genomic analysis identified a circular double-stranded DNA genome, closely related to the <i>Aeromonas</i> phage pAEv1812 (ID: OL964754.1), with UniProtKB-based functional annotation categorizing encoded proteins into DNA modification and structural classes. COG and KEGG analyses further demonstrated gene enrichment in nucleic acid metabolism and purine biosynthesis, consistent with phage replication machinery. Crucially, virulence factor screening confirmed the absence of resistance or virulence genes, ensuring genetic-level biosafety. <i>In vitro</i> antimicrobial tests showed that phage pAEv1 effectively inhibited <i>A. veronii</i>. Additionally, <i>in vivo</i> experiments demonstrated that grass carp treated with pAEv1 had an 80% survival rate after 7 days of exposure to a double minimum lethal dose (MLD) of the bacterium.
DOI: 10.6084/m9.figshare.30120499
title: Viral driving force on virulence differentiation of a rice phytopathogenic fungus and the implication for biocontrol

description: Viruses are the most abundant biological entities in natural environments. Mycoviruses or fungal viruses are viruses that infect fungi and are being increasingly recognized. However, their ecological function in regulating microbial communities is not well understood. Here, we analyzed the differentiation of the biological characteristics of 32 <i>Rhizoctonia solani</i> strains isolated from rice and confirmed that there was obvious differentiation, especially in virulence. Screening of dsRNA and sequence determination showed that all 32 strains carried viruses displaying a high virus-carrying rate, which was composed of a diverse variety of mycoviruses showing genetic relationships with 15 different families and unclassified virus. In addition, we conducted experiments on multiple horizontal viral infections via hyphal anastomosis between different strains, a simulated ecological environment in a culture dish, and evaluated the dsRNA profiles and virulence of the derivative strains. The results revealed that <i>R. solani</i> strains might suffer multiple infections of mycoviruses via mycelial contact between a multitude of strains and lead to virulence differentiation, thus confirming that mycoviruses are an important driving force of virulence differentiation in this fungus. Moreover, a hypovirulent strain, DWZ-6, was obtained via multiple horizontal viral transfers. Overall, this study provides insights into the ecological implications of mycovirus infection in the virulence differentiation of plant pathogenic fungi and the means of obtaining hypovirulent strains with biological control potential, all of which might serve as a basis for monitoring epidemics of fungal plant disease and developing an environmentally friendly biological control approach.
DOI: 10.6084/m9.figshare.30120499.v1
title: Viral driving force on virulence differentiation of a rice phytopathogenic fungus and the implication for biocontrol

description: Viruses are the most abundant biological entities in natural environments. Mycoviruses or fungal viruses are viruses that infect fungi and are being increasingly recognized. However, their ecological function in regulating microbial communities is not well understood. Here, we analyzed the differentiation of the biological characteristics of 32 <i>Rhizoctonia solani</i> strains isolated from rice and confirmed that there was obvious differentiation, especially in virulence. Screening of dsRNA and sequence determination showed that all 32 strains carried viruses displaying a high virus-carrying rate, which was composed of a diverse variety of mycoviruses showing genetic relationships with 15 different families and unclassified virus. In addition, we conducted experiments on multiple horizontal viral infections via hyphal anastomosis between different strains, a simulated ecological environment in a culture dish, and evaluated the dsRNA profiles and virulence of the derivative strains. The results revealed that <i>R. solani</i> strains might suffer multiple infections of mycoviruses via mycelial contact between a multitude of strains and lead to virulence differentiation, thus confirming that mycoviruses are an important driving force of virulence differentiation in this fungus. Moreover, a hypovirulent strain, DWZ-6, was obtained via multiple horizontal viral transfers. Overall, this study provides insights into the ecological implications of mycovirus infection in the virulence differentiation of plant pathogenic fungi and the means of obtaining hypovirulent strains with biological control potential, all of which might serve as a basis for monitoring epidemics of fungal plant disease and developing an environmentally friendly biological control approach.