cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30120529.v1
title: Novel strategies for PEDV to interfere with host antiviral immunity through Caspase-1

description: Porcine epidemic diarrhea virus (PEDV), a member of the <i>Coronaviridae</i> family, responsible for substantial morbidity and mortality in neonatal piglets, representing an ongoing threat to the swine industry. The type I interferon (IFN) response is integral to the innate immune system, playing a critical role in host defense against viral infection. However, viruses have evolved diverse strategies to evade or suppress host immune responses to facilitate their replication. In this study, we demonstrate that PEDV targets Caspase-1 to enhance its replication and suppress IFN-β production. PEDV infection increases the expression of Caspase-1 in both tissues and cells. Overexpression of Caspase-1 significantly reduces IFN-β production while promoting PEDV replication. The suppression of IFN-β production by Caspase-1 is mediated through the cleavage of mitochondrial antiviral signaling (MAVS). Specifically, Caspase-1 cleaves MAVS at Asp182, facilitating viral replication and inhibiting IFN-β production. The resulting MAVS fragments, once cleaved, lose their ability to both inhibit viral replication and induce IFN-β production, thereby enabling PEDV proliferation. Additionally, we observe that Caspase-1 exhibits species-specific cleavage effects on MAVS, though its impact on MAVS cleavage remains consistent. This study provides a novel target for anti-PEDV therapeutic strategies.
DOI: 10.6084/m9.figshare.29422974
title: <i>Streptococcus suis</i> serotype 5: Emerging zoonotic threat with distinct genomic heterogeneity

description: <i>Streptococcus suis</i> is a significant pig pathogen and an emerging zoonotic agent. Serotype 5 is becoming an increasing concern among pigs and humans with <i>S. suis</i> infection worldwide. This study investigated the population structure, phylogenetic relationship, genomic characteristics, and virulence of serotype 5 population, analyzing 89 isolates, including eight from human cases. The results revealed significant genomic heterogeneity and diverse virulence levels within serotype 5 population. Phylogenetic analysis identified two distinct lineages with notable differences in evolution and genomic traits. Thirty-two representative serotype 5 strains were clustered into four groups: ultra-highly virulent (UV) (<i>n</i> = 1), highly virulent plus (HV<sup>+</sup>) (<i>n</i> = 4), HV (<i>n</i> = 11), and virulent (V) (<i>n</i> = 16). Virulence levels progressively decreased from the UV group to HV<sup>+</sup>, HV, and V groups. The UV, HV<sup>+</sup>, and HV strains induced significantly lethal infection in mice during the early phase of infection. The lethal infection induced by UV and HV<sup>+</sup> strains was time-dependent but dose-independent. Ultra-high bacterial loads, excessive pro-inflammatory cytokines, and severe organ damage were responsible for the sudden death of mice infected with UV strain at the early phase of infection. The capacity to establish infection, induce excessive pro-inflammatory cytokine production, and elevate biomarkers associated with organ damage varied significantly among HV<sup>+</sup> strains. The V strains demonstrated the capacity to induce delayed lethal infection. These findings emphasized the serious public health risk posed by serotype 5 strains. The valuable information for developing effective prevention and control strategies for <i>S. suis</i> serotype 5 infections was provided.
DOI: 10.6084/m9.figshare.29422974.v1
title: <i>Streptococcus suis</i> serotype 5: Emerging zoonotic threat with distinct genomic heterogeneity

description: <i>Streptococcus suis</i> is a significant pig pathogen and an emerging zoonotic agent. Serotype 5 is becoming an increasing concern among pigs and humans with <i>S. suis</i> infection worldwide. This study investigated the population structure, phylogenetic relationship, genomic characteristics, and virulence of serotype 5 population, analyzing 89 isolates, including eight from human cases. The results revealed significant genomic heterogeneity and diverse virulence levels within serotype 5 population. Phylogenetic analysis identified two distinct lineages with notable differences in evolution and genomic traits. Thirty-two representative serotype 5 strains were clustered into four groups: ultra-highly virulent (UV) (<i>n</i> = 1), highly virulent plus (HV<sup>+</sup>) (<i>n</i> = 4), HV (<i>n</i> = 11), and virulent (V) (<i>n</i> = 16). Virulence levels progressively decreased from the UV group to HV<sup>+</sup>, HV, and V groups. The UV, HV<sup>+</sup>, and HV strains induced significantly lethal infection in mice during the early phase of infection. The lethal infection induced by UV and HV<sup>+</sup> strains was time-dependent but dose-independent. Ultra-high bacterial loads, excessive pro-inflammatory cytokines, and severe organ damage were responsible for the sudden death of mice infected with UV strain at the early phase of infection. The capacity to establish infection, induce excessive pro-inflammatory cytokine production, and elevate biomarkers associated with organ damage varied significantly among HV<sup>+</sup> strains. The V strains demonstrated the capacity to induce delayed lethal infection. These findings emphasized the serious public health risk posed by serotype 5 strains. The valuable information for developing effective prevention and control strategies for <i>S. suis</i> serotype 5 infections was provided.
DOI: 10.6084/m9.figshare.29606067
title: Prevalence and clinical significance of HBeAg-positive chronic hepatitis B patients with and without anti-HBe antibody

description: The clinical significance of the coexistence of hepatitis B e antigen (HBeAg) and antibodies against HBeAg (anti-HBe) in patients with chronic hepatitis B (CHB) remains unclear. This study investigated the clinical features and phase transition of patients with coexisting HBeAg/anti-HBe. A total of 840 treatment-naïve HBeAg-positive CHB patients from two medical centres were included. Cox regression analysis was used to analyze factors associated with HBeAg clearance and seroconversion. Eighty-six patients (10.2%) had coexisting HBeAg/anti-HBe. Patients with anti-HBe were older (39.0 vs. 34.0 years, <i>p</i>=0.016) and had a higher FIB-4 values (1.5 vs. 1.0, <i>p</i>&lt;0.001) than those without anti-HBe. The proportions of HBeAg clearance (41.9% vs. 16.2%, <i>p</i>&lt;0.001) and HBeAg seroconversion (37.2% vs. 11.4%, <i>p</i>&lt;0.001) were significantly higher in patients with coexisting HBeAg/anti-HBe than in those without anti-HBe during the follow-up period. Surprisingly, 39.5% of patients with anti-HBe transitioned to HBeAg-positive and anti-HBe-negative status. A total of 4.7% of patients with HBeAg and anti-HBe coexistence transitioned to HBeAg-negative and anti-HBe-negative status. Patients with anti-HBe had higher cumulative HBeAg clearance and seroconversion rates than those without anti-HBe (<i>p</i>&lt;0.001). HBeAg/anti-HBe coexistence was associated with higher HBeAg clearance (HR 2.960, 95%CI 1.828–4.791, <i>p</i>&lt;0.001) and HBeAg seroconversion (HR 4.018, 95% CI 2.372–6.805, <i>p</i>&lt;0.001). Patients with coexisting HBeAg and anti-HBe had a higher likelihood of HBeAg clearance and seroconversion. Close follow-up is needed to monitor the phase transitions in patients with coexistence of HBeAg and anti-HBe patients.
DOI: 10.6084/m9.figshare.29606067.v1
title: Prevalence and clinical significance of HBeAg-positive chronic hepatitis B patients with and without anti-HBe antibody

description: The clinical significance of the coexistence of hepatitis B e antigen (HBeAg) and antibodies against HBeAg (anti-HBe) in patients with chronic hepatitis B (CHB) remains unclear. This study investigated the clinical features and phase transition of patients with coexisting HBeAg/anti-HBe. A total of 840 treatment-naïve HBeAg-positive CHB patients from two medical centres were included. Cox regression analysis was used to analyze factors associated with HBeAg clearance and seroconversion. Eighty-six patients (10.2%) had coexisting HBeAg/anti-HBe. Patients with anti-HBe were older (39.0 vs. 34.0 years, <i>p</i>=0.016) and had a higher FIB-4 values (1.5 vs. 1.0, <i>p</i>&lt;0.001) than those without anti-HBe. The proportions of HBeAg clearance (41.9% vs. 16.2%, <i>p</i>&lt;0.001) and HBeAg seroconversion (37.2% vs. 11.4%, <i>p</i>&lt;0.001) were significantly higher in patients with coexisting HBeAg/anti-HBe than in those without anti-HBe during the follow-up period. Surprisingly, 39.5% of patients with anti-HBe transitioned to HBeAg-positive and anti-HBe-negative status. A total of 4.7% of patients with HBeAg and anti-HBe coexistence transitioned to HBeAg-negative and anti-HBe-negative status. Patients with anti-HBe had higher cumulative HBeAg clearance and seroconversion rates than those without anti-HBe (<i>p</i>&lt;0.001). HBeAg/anti-HBe coexistence was associated with higher HBeAg clearance (HR 2.960, 95%CI 1.828–4.791, <i>p</i>&lt;0.001) and HBeAg seroconversion (HR 4.018, 95% CI 2.372–6.805, <i>p</i>&lt;0.001). Patients with coexisting HBeAg and anti-HBe had a higher likelihood of HBeAg clearance and seroconversion. Close follow-up is needed to monitor the phase transitions in patients with coexistence of HBeAg and anti-HBe patients.
DOI: 10.6084/m9.figshare.30505741
title: Master transcriptional regulator SaeS in <i>Staphylococcus aureus</i> contributes to staphyloxanthin biosynthesis to promote survival during invasive infection

description: <i>Staphylococcus aureus</i> is a major human opportunistic pathogen that causes significant morbidity and mortality, particularly in immunocompromised individuals. SaeRS is a two-component system in <i>S. aureus</i> that regulates signal transduction related to virulence, including hemolysis and coagulation. Metal ions are essential nutrients that support bacterial virulence and survival against host immune cells and are intricately interconnected with regulatory systems. The SaeRS system has long been studied for its function in bacterial virulence and invasive infections. However, its interactions with other regulators and metal ions remain unelucidated. Thus, this study evaluated the effects of the <i>S. aureus</i> SaeRS system on virulence, specifically its association with oxidative stress resistance and staphyloxanthin (STX) production. <i>saeS</i> deletion reduced STX production via the SigB-CrtOPQMN pathway, increasing vulnerability to oxidative stress and susceptibility to host immune cells. Supplementation with metal ions, specifically zinc, inhibited STX-associated gene expression, attenuating antioxidative activity <i>in vitro</i>. Experiments on mice with <i>S. aureus</i> bloodstream infection verified that SaeS was crucial for bacterial survival <i>in vivo</i>. Furthermore, zinc contributed to weakened bacterial virulence and altered host immune defense mechanisms. Collectively, our results established a novel mechanistic interconnection between SaeRS and STX biosynthesis and demonstrated that SaeRS inhibition combined with zinc supplementation promotes innate immune system-mediated killing of <i>S. aureus</i>.
DOI: 10.6084/m9.figshare.30505741.v1
title: Master transcriptional regulator SaeS in <i>Staphylococcus aureus</i> contributes to staphyloxanthin biosynthesis to promote survival during invasive infection

description: <i>Staphylococcus aureus</i> is a major human opportunistic pathogen that causes significant morbidity and mortality, particularly in immunocompromised individuals. SaeRS is a two-component system in <i>S. aureus</i> that regulates signal transduction related to virulence, including hemolysis and coagulation. Metal ions are essential nutrients that support bacterial virulence and survival against host immune cells and are intricately interconnected with regulatory systems. The SaeRS system has long been studied for its function in bacterial virulence and invasive infections. However, its interactions with other regulators and metal ions remain unelucidated. Thus, this study evaluated the effects of the <i>S. aureus</i> SaeRS system on virulence, specifically its association with oxidative stress resistance and staphyloxanthin (STX) production. <i>saeS</i> deletion reduced STX production via the SigB-CrtOPQMN pathway, increasing vulnerability to oxidative stress and susceptibility to host immune cells. Supplementation with metal ions, specifically zinc, inhibited STX-associated gene expression, attenuating antioxidative activity <i>in vitro</i>. Experiments on mice with <i>S. aureus</i> bloodstream infection verified that SaeS was crucial for bacterial survival <i>in vivo</i>. Furthermore, zinc contributed to weakened bacterial virulence and altered host immune defense mechanisms. Collectively, our results established a novel mechanistic interconnection between SaeRS and STX biosynthesis and demonstrated that SaeRS inhibition combined with zinc supplementation promotes innate immune system-mediated killing of <i>S. aureus</i>.
DOI: 10.6084/m9.figshare.30031142
title: <i>Cryptosporidium</i> exports a mucin glycoprotein into the microvilli of intestinal epithelium

description: <i>Cryptosporidium</i> causes severe diarrhea in humans and animals. Mucin-like glycoproteins play a critical role in parasite attachment and invasion and therefore serve as potential protective antigens against reinfection. Muc25 is a highly polymorphic mucin that has been associated with differences in host infectivity in comparative genomic analyses. To study the function of Muc25, we determined its localization and secretion in <i>Cryptosporidium parvum</i> by genome editing. Endogenous gene tagging revealed that Muc25 is stored in small granules of sporozoites and secreted into host microvilli after invasion. Deletion of the signal peptide affected Muc25 localization and secretion, as the Muc25ΔSP protein was localized to the membrane in sporozoites and remained within intracellular life stages. In addition, a <i>Muc25</i> knockout strain (<i>ΔMuc25</i>) was easily generated, indicating that Muc25 is not critical for parasite survival. However, the <i>ΔMuc25</i> strain showed reduced growth in HCT-8 cells, and the survival time was prolonged in GKO mice infected with <i>ΔMuc25</i> compared to those infected with Muc25–3 HA. Transcriptome analysis revealed that <i>ΔMuc25</i> parasites caused less damage to host cells <i>in vitro</i> than Muc25–3 HA parasites. Taken together, these data provide evidence for the export of a <i>Cryptosporidium</i> protein to host microvilli and demonstrate that such manipulation of the host cell response may be involved in parasite pathogenesis.
DOI: 10.6084/m9.figshare.30031142.v1
title: <i>Cryptosporidium</i> exports a mucin glycoprotein into the microvilli of intestinal epithelium

description: <i>Cryptosporidium</i> causes severe diarrhea in humans and animals. Mucin-like glycoproteins play a critical role in parasite attachment and invasion and therefore serve as potential protective antigens against reinfection. Muc25 is a highly polymorphic mucin that has been associated with differences in host infectivity in comparative genomic analyses. To study the function of Muc25, we determined its localization and secretion in <i>Cryptosporidium parvum</i> by genome editing. Endogenous gene tagging revealed that Muc25 is stored in small granules of sporozoites and secreted into host microvilli after invasion. Deletion of the signal peptide affected Muc25 localization and secretion, as the Muc25ΔSP protein was localized to the membrane in sporozoites and remained within intracellular life stages. In addition, a <i>Muc25</i> knockout strain (<i>ΔMuc25</i>) was easily generated, indicating that Muc25 is not critical for parasite survival. However, the <i>ΔMuc25</i> strain showed reduced growth in HCT-8 cells, and the survival time was prolonged in GKO mice infected with <i>ΔMuc25</i> compared to those infected with Muc25–3 HA. Transcriptome analysis revealed that <i>ΔMuc25</i> parasites caused less damage to host cells <i>in vitro</i> than Muc25–3 HA parasites. Taken together, these data provide evidence for the export of a <i>Cryptosporidium</i> protein to host microvilli and demonstrate that such manipulation of the host cell response may be involved in parasite pathogenesis.
DOI: 10.6084/m9.figshare.30371487
title: Human bocavirus NP1 antagonizes host type I interferon response through repressing the nuclear transport of STAT1

description: Human bocavirus 1 (HBoV1), first identified in human nasopharyngeal specimens in 2005, is a relatively recent member of the respiratory virus family and is primarily associated with respiratory tract infections. Despite this, the mechanisms underlying HBoV1 pathogenesis remain poorly understood, primarily due to the lack of suitable cell lines and animal models, as well as the complicating factor of co-infections with other pathogens. In this study, we demonstrate that the non-structural protein 1 (NP1) of HBoV1 antagonizes the type I interferon (IFN-I) signaling pathway. NP1 interacts with the DNA-binding domain (DBD) of signal transducer and activator of transcription 1 (STAT1) and the importing β-binding (IBB) domain of karyopherin subunit alpha-1 (KPNA1), thereby disrupting the formation of the STAT1/KPNA1/KPNB1 complex and subsequently inhibiting STAT1 nuclear translocation, a critical step in IFN-I signaling. Furthermore, we show that HBoV1 NP1 facilitates the replication of influenza A virus (IAV) and respiratory syncytial virus (RSV). These findings suggest a novel mechanism by which bocavirus proteins antagonize the host’s innate immune response and provide new evidence that bocavirus may exacerbate the symptoms of clinical respiratory viral infections.
DOI: 10.6084/m9.figshare.30371487.v1
title: Human bocavirus NP1 antagonizes host type I interferon response through repressing the nuclear transport of STAT1

description: Human bocavirus 1 (HBoV1), first identified in human nasopharyngeal specimens in 2005, is a relatively recent member of the respiratory virus family and is primarily associated with respiratory tract infections. Despite this, the mechanisms underlying HBoV1 pathogenesis remain poorly understood, primarily due to the lack of suitable cell lines and animal models, as well as the complicating factor of co-infections with other pathogens. In this study, we demonstrate that the non-structural protein 1 (NP1) of HBoV1 antagonizes the type I interferon (IFN-I) signaling pathway. NP1 interacts with the DNA-binding domain (DBD) of signal transducer and activator of transcription 1 (STAT1) and the importing β-binding (IBB) domain of karyopherin subunit alpha-1 (KPNA1), thereby disrupting the formation of the STAT1/KPNA1/KPNB1 complex and subsequently inhibiting STAT1 nuclear translocation, a critical step in IFN-I signaling. Furthermore, we show that HBoV1 NP1 facilitates the replication of influenza A virus (IAV) and respiratory syncytial virus (RSV). These findings suggest a novel mechanism by which bocavirus proteins antagonize the host’s innate immune response and provide new evidence that bocavirus may exacerbate the symptoms of clinical respiratory viral infections.
DOI: 10.6084/m9.figshare.29041335
title: LncRNA transcriptome analysis of rainbow trout (<i>Oncorhynchus mykiss</i>) skin infected with IHNV reveals that lncRNA SARL/miR-205-z/<i>SOCS3</i> axis negatively regulates antiviral immunity mechanisms

description: Long non-coding RNAs (lncRNAs) are new gene regulators involved in various biological processes. However, the regulatory effect of lncRNA on the rainbow trout (<i>Oncorhynchus mykiss</i>) antiviral immune response has not been reported. Here, we measured lncRNA profiles at 48 hpi compared to the control group, expression levels of lncRNA, miRNA, and gene, and lncRNA SARL/miR-205-z/<i>SOCS3</i> functions after rainbow trout skin infected with infectious haematopoietic necrosis virus (IHNV) by RNA-seq, qRT-PCR, and overexpression and inhibition assays. Transcriptome analysis identified twelve upregulated and four downregulated DElncRNAs. Twelve key immune-related competing endogenous RNA (ceRNA) networks were identified, and the target genes were enriched in the TLR, RLR, NLR, and p53 signalling pathways. Expression patterns suggested that changes in lncRNA SARL, miR-205-z, and <i>SOCS3</i> expression presented a ceRNA regulatory relationship. Further studies demonstrated that the lncRNA SARL was a ceRNA of <i>SOCS3</i> by sponging miR-205-z <i>in vitro</i>, thereby playing a negative regulatory role in the antiviral immune response of rainbow trout. We also found that miR-205-z was a positive regulator of rainbow trout liver cell proliferation, and this effect could be reversed by <i>SOCS3</i>. <i>In vivo</i>, <i>SOCS3</i> expression significantly increased after antagomiR-205-z injection. Furthermore, <i>SOCS3</i> overexpression significantly promoted the replication of IHNV. This study provides fundamental data for disease resistance breeding and targeted drug therapy in rainbow trout.
DOI: 10.6084/m9.figshare.29041335.v1
title: LncRNA transcriptome analysis of rainbow trout (<i>Oncorhynchus mykiss</i>) skin infected with IHNV reveals that lncRNA SARL/miR-205-z/<i>SOCS3</i> axis negatively regulates antiviral immunity mechanisms

description: Long non-coding RNAs (lncRNAs) are new gene regulators involved in various biological processes. However, the regulatory effect of lncRNA on the rainbow trout (<i>Oncorhynchus mykiss</i>) antiviral immune response has not been reported. Here, we measured lncRNA profiles at 48 hpi compared to the control group, expression levels of lncRNA, miRNA, and gene, and lncRNA SARL/miR-205-z/<i>SOCS3</i> functions after rainbow trout skin infected with infectious haematopoietic necrosis virus (IHNV) by RNA-seq, qRT-PCR, and overexpression and inhibition assays. Transcriptome analysis identified twelve upregulated and four downregulated DElncRNAs. Twelve key immune-related competing endogenous RNA (ceRNA) networks were identified, and the target genes were enriched in the TLR, RLR, NLR, and p53 signalling pathways. Expression patterns suggested that changes in lncRNA SARL, miR-205-z, and <i>SOCS3</i> expression presented a ceRNA regulatory relationship. Further studies demonstrated that the lncRNA SARL was a ceRNA of <i>SOCS3</i> by sponging miR-205-z <i>in vitro</i>, thereby playing a negative regulatory role in the antiviral immune response of rainbow trout. We also found that miR-205-z was a positive regulator of rainbow trout liver cell proliferation, and this effect could be reversed by <i>SOCS3</i>. <i>In vivo</i>, <i>SOCS3</i> expression significantly increased after antagomiR-205-z injection. Furthermore, <i>SOCS3</i> overexpression significantly promoted the replication of IHNV. This study provides fundamental data for disease resistance breeding and targeted drug therapy in rainbow trout.