cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.20524685.v2
title: SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism

description: As obligate intracellular parasites, viruses rely completely on host metabolic machinery and hijack host nutrients for viral replication. Newcastle disease virus (NDV) causes acute, highly contagious avian disease and functions as an oncolytic agent. NDV efficiently replicates in both chicken and tumour cells. However, how NDV reprograms host cellular metabolism for its efficient replication is still ill-defined. We previously identified a significantly upregulated glutamate transporter gene, solute carrier family 1 member 3 (<i>SLC1A3</i>), during NDV infection via transcriptome analysis. To investigate the potential role of <i>SLC1A3</i> during NDV infection, we first confirmed the marked upregulation of <i>SLC1A3</i> in NDV-infected DF-1 or A549 cells through p53 and NF-κB pathways. Knockdown of <i>SLC1A3</i> inhibited NDV infection. Western blot analysis further confirmed that glutamine, but not glutamate, asparagine, or aspartate, was required for NDV replication. Metabolic flux data showed that NDV promotes the decomposition of glutamine into the tricarboxylic acid cycle. Importantly, the level of glutamate and glutaminolysis were reduced by <i>SLC1A3</i> knockdown, indicating that <i>SLC1A3</i> propelled glutaminolysis for glutamate utilization and NDV replication in host cells. Taken together, our data identify that <i>SLC1A3</i> serves as an important regulator for glutamine metabolism and is hijacked by NDV for its efficient replication during NDV infection. These results improve our understanding of the interaction between NDV and host cellular metabolism and lay the foundation for further investigation of efficient vaccines.
DOI: 10.6084/m9.figshare.19130005
title: Differential expression of long non-coding RNAs under <i>Peste des petits ruminants virus</i> (PPRV) infection in goats

description: <i>Peste des petits ruminants</i> (PPR) characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and pneumonia, is an acute, highly contagious viral disease of sheep and goats. The role of long non-coding RNAs (lncRNAs) in PPRV infection has not been explored to date. In this study, the transcriptome profiles of virulent Peste des petits ruminants virus (PPRV) infected goat tissues – lung and spleen were analyzed to identify the role of lncRNAs in PPRV infection. A total of 13,928 lncRNA transcripts were identified, out of which 170 were known lncRNAs. Intergenic lncRNAs (7625) formed the major chunk of the novel lncRNA transcripts. Differential expression analysis revealed that 15 lncRNAs (11 downregulated and 4 upregulated) in the PPRV infected spleen samples and 16 lncRNAs (13 downregulated and 3 upregulated) in PPRV infected lung samples were differentially expressed as compared to control. The differentially expressed lncRNAs (DElncRNAs) possibly regulate various immunological processes related to natural killer cell activation, antigen processing and presentation, and B cell activity, by regulating the expression of mRNAs through the cis- or trans-regulatory mechanism. Functional enrichment analysis of differentially expressed mRNAs (DEmRNAs) revealed enrichment of immune pathways and biological processes in concordance with the pathways in which correlated lncRNA-neighboring genes were enriched. The results suggest that a coordinated immune response is raised in both lung and spleen tissues of the goat through mRNA-lncRNA crosstalk.
DOI: 10.6084/m9.figshare.19130005.v1
title: Differential expression of long non-coding RNAs under <i>Peste des petits ruminants virus</i> (PPRV) infection in goats

description: <i>Peste des petits ruminants</i> (PPR) characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and pneumonia, is an acute, highly contagious viral disease of sheep and goats. The role of long non-coding RNAs (lncRNAs) in PPRV infection has not been explored to date. In this study, the transcriptome profiles of virulent Peste des petits ruminants virus (PPRV) infected goat tissues – lung and spleen were analyzed to identify the role of lncRNAs in PPRV infection. A total of 13,928 lncRNA transcripts were identified, out of which 170 were known lncRNAs. Intergenic lncRNAs (7625) formed the major chunk of the novel lncRNA transcripts. Differential expression analysis revealed that 15 lncRNAs (11 downregulated and 4 upregulated) in the PPRV infected spleen samples and 16 lncRNAs (13 downregulated and 3 upregulated) in PPRV infected lung samples were differentially expressed as compared to control. The differentially expressed lncRNAs (DElncRNAs) possibly regulate various immunological processes related to natural killer cell activation, antigen processing and presentation, and B cell activity, by regulating the expression of mRNAs through the cis- or trans-regulatory mechanism. Functional enrichment analysis of differentially expressed mRNAs (DEmRNAs) revealed enrichment of immune pathways and biological processes in concordance with the pathways in which correlated lncRNA-neighboring genes were enriched. The results suggest that a coordinated immune response is raised in both lung and spleen tissues of the goat through mRNA-lncRNA crosstalk.
DOI: 10.6084/m9.figshare.19925807
title: Plant pathogens provide clues to the potential origin of bat white-nose syndrome <i>Pseudogymnoascus destructans</i>

description: White-nose syndrome has killed millions of bats, yet both the origins and infection strategy of the causative fungus, <i>Pseudogymnoascus destructans</i>, remain elusive. We provide evidence for a novel hypothesis that <i>P. destructans</i> emerged from plant-associated fungi and retained invasion strategies affiliated with fungal pathogens of plants. We demonstrate that <i>P. destructans</i> invades bat skin in successive biotrophic and necrotrophic stages (hemibiotrophic infection), a mechanism previously only described in plant fungal pathogens. Further, the convergence of hyphae at hair follicles suggests nutrient tropism. Tropism, biotrophy, and necrotrophy are often associated with structures termed appressoria in plant fungal pathogens; the penetrating hyphae produced by <i>P. destructans</i> resemble appressoria. Finally, we conducted a phylogenomic analysis of a taxonomically diverse collection of fungi. Despite gaps in genetic sampling of prehistoric and contemporary fungal species, we estimate an 88% probability the ancestral state of the clade containing <i>P. destructans</i> was a plant-associated fungus.
DOI: 10.6084/m9.figshare.19925807.v1
title: Plant pathogens provide clues to the potential origin of bat white-nose syndrome <i>Pseudogymnoascus destructans</i>

description: White-nose syndrome has killed millions of bats, yet both the origins and infection strategy of the causative fungus, <i>Pseudogymnoascus destructans</i>, remain elusive. We provide evidence for a novel hypothesis that <i>P. destructans</i> emerged from plant-associated fungi and retained invasion strategies affiliated with fungal pathogens of plants. We demonstrate that <i>P. destructans</i> invades bat skin in successive biotrophic and necrotrophic stages (hemibiotrophic infection), a mechanism previously only described in plant fungal pathogens. Further, the convergence of hyphae at hair follicles suggests nutrient tropism. Tropism, biotrophy, and necrotrophy are often associated with structures termed appressoria in plant fungal pathogens; the penetrating hyphae produced by <i>P. destructans</i> resemble appressoria. Finally, we conducted a phylogenomic analysis of a taxonomically diverse collection of fungi. Despite gaps in genetic sampling of prehistoric and contemporary fungal species, we estimate an 88% probability the ancestral state of the clade containing <i>P. destructans</i> was a plant-associated fungus.
DOI: 10.6084/m9.figshare.20524685.v1
title: SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism

description: As obligate intracellular parasites, viruses rely completely on host metabolic machinery and hijack host nutrients for viral replication. Newcastle disease virus (NDV) causes acute, highly contagious avian disease and functions as an oncolytic agent. NDV efficiently replicates in both chicken and tumour cells. However, how NDV reprograms host cellular metabolism for its efficient replication is still ill-defined. We previously identified a significantly upregulated glutamate transporter gene, solute carrier family 1 member 3 (<i>SLC1A3</i>), during NDV infection via transcriptome analysis. To investigate the potential role of <i>SLC1A3</i> during NDV infection, we first confirmed the marked upregulation of <i>SLC1A3</i> in NDV-infected DF-1 or A549 cells through p53 and NF-κB pathways. Knockdown of <i>SLC1A3</i> inhibited NDV infection. Western blot analysis further confirmed that glutamine, but not glutamate, asparagine, or aspartate, was required for NDV replication. Metabolic flux data showed that NDV promotes the decomposition of glutamine into the tricarboxylic acid cycle. Importantly, the level of glutamate and glutaminolysis were reduced by <i>SLC1A3</i> knockdown, indicating that <i>SLC1A3</i> propelled glutaminolysis for glutamate utilization and NDV replication in host cells. Taken together, our data identify that <i>SLC1A3</i> serves as an important regulator for glutamine metabolism and is hijacked by NDV for its efficient replication during NDV infection. These results improve our understanding of the interaction between NDV and host cellular metabolism and lay the foundation for further investigation of efficient vaccines.
DOI: 10.6084/m9.figshare.21262164
title: High frequency of CD8 escape mutations in elite controllers as new obstacle for HIV cure

description: Accumulation of mutations in epitopes of cytolytic-<i>T</i>-lymphocytes immune response (CTL) in HIV-reservoir seems to be one of the reasons for shock-and-kill strategy failure. Ten non-controller patients on successful cART (TX) and seven elite controllers (EC) were included. HIV-Gag gene from purified resting memory CD4+ <i>T</i>-cells was sequenced by Next-Generation-Sequencing. HLA class-I alleles were typed to predict optimal HIV-Gag CTL epitopes. For each subject, the frequency of mutated epitopes in the HIV-Gag gene, the proportion of them considered as CTL-escape variants as well as their effect on antigen recognition by HLA were assessed. The proportion (%) of mutated HIV-Gag CTL epitopes in the reservoir was high and similar in EC and TX (86%[50–100] and 57%[48–82] respectively, p=0.315). Many of them were predicted to negatively impact antigen recognition. Moreover, the proportion of mutated epitopes considered to be CTL-escape variants was also similar in TX and EC (77%[49–92] vs. 50%[33–75] respectively, p=0.117). Thus, the most relevant finding of our study was the high and similar proportions of HIV-Gag CTL-escape mutations in the reservoir of both HIV-noncontroller patients with cART (TX) and patients with spontaneous HIV-control (EC). Our findings suggest that escape mutations of CTL-response may be another obstacle to eliminate the HIV reservoir and constitute a proof of concept that challenges HIV cure strategies focused on the reactivation of reservoirs. Due to the small sample size that could impact the robustness of the study, further studies with larger cohorts of elite controller patients are needed to confirm these results.
DOI: 10.6084/m9.figshare.21262164.v1
title: High frequency of CD8 escape mutations in elite controllers as new obstacle for HIV cure

description: Accumulation of mutations in epitopes of cytolytic-<i>T</i>-lymphocytes immune response (CTL) in HIV-reservoir seems to be one of the reasons for shock-and-kill strategy failure. Ten non-controller patients on successful cART (TX) and seven elite controllers (EC) were included. HIV-Gag gene from purified resting memory CD4+ <i>T</i>-cells was sequenced by Next-Generation-Sequencing. HLA class-I alleles were typed to predict optimal HIV-Gag CTL epitopes. For each subject, the frequency of mutated epitopes in the HIV-Gag gene, the proportion of them considered as CTL-escape variants as well as their effect on antigen recognition by HLA were assessed. The proportion (%) of mutated HIV-Gag CTL epitopes in the reservoir was high and similar in EC and TX (86%[50–100] and 57%[48–82] respectively, p=0.315). Many of them were predicted to negatively impact antigen recognition. Moreover, the proportion of mutated epitopes considered to be CTL-escape variants was also similar in TX and EC (77%[49–92] vs. 50%[33–75] respectively, p=0.117). Thus, the most relevant finding of our study was the high and similar proportions of HIV-Gag CTL-escape mutations in the reservoir of both HIV-noncontroller patients with cART (TX) and patients with spontaneous HIV-control (EC). Our findings suggest that escape mutations of CTL-response may be another obstacle to eliminate the HIV reservoir and constitute a proof of concept that challenges HIV cure strategies focused on the reactivation of reservoirs. Due to the small sample size that could impact the robustness of the study, further studies with larger cohorts of elite controller patients are needed to confirm these results.
DOI: 10.6084/m9.figshare.19689146
title: Vaccination inducing durable and robust antigen-specific Th1/Th17 immune responses contributes to prophylactic protection against <i>Mycobacterium avium</i> infection but is ineffective as an adjunct to antibiotic treatment in chronic disease

description: <i>Mycobacterium avium</i> complex (MAC) causing pulmonary disease in humanshas emerged worldwide. Thus, effective strategies simultaneously aiming to prevent MAC infection and accelerate therapeutic efficacy are required. To this end, subunit vaccine-induced protection against a well-defined virulent <i>Mycobacterium avium</i> (Mav) isolate was assessed as a preventative and therapeutic modality in murine models. Mav-derived culture filtrate antigen (CFA) was used as a vaccine antigen with glucopyranosyl lipid A stable emulsion (GLA-SE) or GLA-SE plus cyclic-di-GMP (GLA-SE/CDG), and we compared the immunogenicities, protective efficacies and immune correlates. Interestingly, CFA+GLA-SE/CDG immunization induced greater CFA-specific Th1/Th17 responses in both the lung and spleen than among the tested groups. Consequently, protective efficacy was optimally achieved with CFA+GLA-SE/CDG by significantly reducing bacterial loads along with long-lasting maintenance of antigen-specific Th1/Th17 cytokine-producing multifunctional T cell responses and relevant cytokine productions. Thus, we employed this subunit vaccine as an adjunct to antibiotic treatment. However, this vaccine was ineffective in further reducing bacterial loads. Collectively, our study demonstrates that strong Mav CFA-specific Th1/Th17 responses are critical for preventative protection against Mav infection but may be ineffective or even detrimental in an established and progressive chronic disease, indicating that different approaches to combating Mav infection are necessary according to vaccination purposes.
DOI: 10.6084/m9.figshare.19689146.v1
title: Vaccination inducing durable and robust antigen-specific Th1/Th17 immune responses contributes to prophylactic protection against <i>Mycobacterium avium</i> infection but is ineffective as an adjunct to antibiotic treatment in chronic disease

description: <i>Mycobacterium avium</i> complex (MAC) causing pulmonary disease in humanshas emerged worldwide. Thus, effective strategies simultaneously aiming to prevent MAC infection and accelerate therapeutic efficacy are required. To this end, subunit vaccine-induced protection against a well-defined virulent <i>Mycobacterium avium</i> (Mav) isolate was assessed as a preventative and therapeutic modality in murine models. Mav-derived culture filtrate antigen (CFA) was used as a vaccine antigen with glucopyranosyl lipid A stable emulsion (GLA-SE) or GLA-SE plus cyclic-di-GMP (GLA-SE/CDG), and we compared the immunogenicities, protective efficacies and immune correlates. Interestingly, CFA+GLA-SE/CDG immunization induced greater CFA-specific Th1/Th17 responses in both the lung and spleen than among the tested groups. Consequently, protective efficacy was optimally achieved with CFA+GLA-SE/CDG by significantly reducing bacterial loads along with long-lasting maintenance of antigen-specific Th1/Th17 cytokine-producing multifunctional T cell responses and relevant cytokine productions. Thus, we employed this subunit vaccine as an adjunct to antibiotic treatment. However, this vaccine was ineffective in further reducing bacterial loads. Collectively, our study demonstrates that strong Mav CFA-specific Th1/Th17 responses are critical for preventative protection against Mav infection but may be ineffective or even detrimental in an established and progressive chronic disease, indicating that different approaches to combating Mav infection are necessary according to vaccination purposes.
DOI: 10.6084/m9.figshare.19673028
title: The antimicrobial systems of <i>Streptococcus suis</i> promote niche competition in pig tonsils

description: <i>Streptococcus suis</i> can cause severe infections in pigs and humans. The tonsils of pigs are major niches for <i>S. suis</i>, and different serotypes of <i>S. suis</i> can be found in the same tonsil. Pig tonsil colonization by <i>S. suis</i> is believed to be an important source of infection for humans and pigs. However, how <i>S. suis</i> competes for a stable tonsil niche is unknown. Here, we found that <i>S. suis</i> strain WUSS351, isolated from a healthy pig tonsil, is virulent and multidrug-resistant. The ABC transporter system SstFEG, conferring resistance to bacitracin, was reported to confer a competitive survival advantage <i>in vivo</i>. In addition, strain WUSS351 has several antimicrobial systems, including a novel type VII secretion system (T7SS), lantibiotic bacteriocin, and lactococcin972-like bacteriocin Lcn351. Bacterial competition experiments demonstrated T7SS-mediated cell contact-dependent antagonism of <i>S. suis</i>. Antibacterial activity analysis and 16S rRNA gene sequencing of the culture-independent and culture-dependent pig tonsillar microbiome revealed that Lcn351 mainly targets <i>S. suis</i>, one of the core microbiomes in pig tonsils. Taken together, our results revealed the mechanism of the stable persistence of <i>S. suis</i> in the tonsil niche, which might have important implications for <i>S. suis</i> epidemiology, potentially influencing strain prevalence and disease progression.
DOI: 10.6084/m9.figshare.19673028.v1
title: The antimicrobial systems of <i>Streptococcus suis</i> promote niche competition in pig tonsils

description: <i>Streptococcus suis</i> can cause severe infections in pigs and humans. The tonsils of pigs are major niches for <i>S. suis</i>, and different serotypes of <i>S. suis</i> can be found in the same tonsil. Pig tonsil colonization by <i>S. suis</i> is believed to be an important source of infection for humans and pigs. However, how <i>S. suis</i> competes for a stable tonsil niche is unknown. Here, we found that <i>S. suis</i> strain WUSS351, isolated from a healthy pig tonsil, is virulent and multidrug-resistant. The ABC transporter system SstFEG, conferring resistance to bacitracin, was reported to confer a competitive survival advantage <i>in vivo</i>. In addition, strain WUSS351 has several antimicrobial systems, including a novel type VII secretion system (T7SS), lantibiotic bacteriocin, and lactococcin972-like bacteriocin Lcn351. Bacterial competition experiments demonstrated T7SS-mediated cell contact-dependent antagonism of <i>S. suis</i>. Antibacterial activity analysis and 16S rRNA gene sequencing of the culture-independent and culture-dependent pig tonsillar microbiome revealed that Lcn351 mainly targets <i>S. suis</i>, one of the core microbiomes in pig tonsils. Taken together, our results revealed the mechanism of the stable persistence of <i>S. suis</i> in the tonsil niche, which might have important implications for <i>S. suis</i> epidemiology, potentially influencing strain prevalence and disease progression.
DOI: 10.6084/m9.figshare.19785260
title: Proteomics analysis reveals a critical role for the WSSV immediate-early protein IE1 in modulating the host prophenoloxidase system

description: White spot syndrome virus (WSSV) is a large, enveloped, double-stranded DNA virus that threatens shrimp aquaculture worldwide. So far, the mechanisms of WSSV-host interactions are ill-defined. Recent studies have revealed that IE1, an immediate-early protein of WSSV, is a multifunctional modulator implicated in virus–host interactions. In this study, the functions of IE1 were further explored by identifying its interacting proteins using GST-pull down and mass spectrometry analysis. A total of 361 host proteins that potentially bind to IE1 were identified. Bioinformatics analysis revealed that the identified IE1-interactors wereinvolved in various signaling pathways such as prophenoloxidase (proPO) system, PI3K-AKT, and MAPK. Among these, the regulatory role of IE1 in shrimp proPO system was further studied. The Co-immunoprecipitation results confirmed that IE1 interacted with the Ig-like domain of <i>Penaeus vannamei</i> proPO or proPO-like protein (hemocyanin). Additionally, we found that knockdown of IE1 reduced viral genes expression and viral loads and increased the hemocytes’ PO activity, whereas recombinant IE1 protein inhibited the PO activity in a dose-dependent manner. Finally, we demonstrated that WSSV could suppress the hemocytes’ PO activity at the early infection stage. Collectively, our current data indicate that IE1 is a novel viral regulator that negatively modulates the shrimp proPO system.
DOI: 10.6084/m9.figshare.19785260.v1
title: Proteomics analysis reveals a critical role for the WSSV immediate-early protein IE1 in modulating the host prophenoloxidase system

description: White spot syndrome virus (WSSV) is a large, enveloped, double-stranded DNA virus that threatens shrimp aquaculture worldwide. So far, the mechanisms of WSSV-host interactions are ill-defined. Recent studies have revealed that IE1, an immediate-early protein of WSSV, is a multifunctional modulator implicated in virus–host interactions. In this study, the functions of IE1 were further explored by identifying its interacting proteins using GST-pull down and mass spectrometry analysis. A total of 361 host proteins that potentially bind to IE1 were identified. Bioinformatics analysis revealed that the identified IE1-interactors wereinvolved in various signaling pathways such as prophenoloxidase (proPO) system, PI3K-AKT, and MAPK. Among these, the regulatory role of IE1 in shrimp proPO system was further studied. The Co-immunoprecipitation results confirmed that IE1 interacted with the Ig-like domain of <i>Penaeus vannamei</i> proPO or proPO-like protein (hemocyanin). Additionally, we found that knockdown of IE1 reduced viral genes expression and viral loads and increased the hemocytes’ PO activity, whereas recombinant IE1 protein inhibited the PO activity in a dose-dependent manner. Finally, we demonstrated that WSSV could suppress the hemocytes’ PO activity at the early infection stage. Collectively, our current data indicate that IE1 is a novel viral regulator that negatively modulates the shrimp proPO system.