cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19984216
title: Natural history of <i>Sudan ebolavirus</i> infection in rhesus and cynomolgus macaques

description: Due to its high mortality rate and continued re-emergence, Ebolavirus disease (EVD) continues to pose a serious threat to global health. A group of viruses within the genus <i>Ebolavirus</i> causes this severe hemorrhagic disease in humans: Ebola virus (EBOV; species <i>Zaire ebolavirus</i>), Sudan virus (SUDV; species <i>Sudan ebolavirus</i>), Bundibugyo virus, and Taï Forest virus. EBOV and SUDV are associated with the highest case fatality rates. While the host response to EBOV has been comprehensively examined, limited data exists for SUDV infection. For medical countermeasure testing, well-characterized SUDV nonhuman primate (NHP) models are thus needed. Here, we describe a natural history study in which rhesus (<i>N</i> = 11) and cynomolgus macaques (<i>N</i> = 14) were intramuscularly exposed to a 1000 plaque-forming unit dose of SUDV (Gulu variant). Time-course analyses of various hematological, pathological, serological, coagulation, and transcriptomic findings are reported. SUDV infection was uniformly lethal in cynomolgus macaques (100% mortality), whereas a single rhesus macaque subject (91% mortality) survived to the study endpoint (median time-to-death of ∼8.0 and ∼8.5 days in cynomolgus and rhesus macaques, respectively). Infected macaques exhibited hallmark features of human EVD. The early stage was typified by viremia, granulocytosis, lymphopenia, albuminemia, thrombocytopenia, and decreased expression of HLA-class transcripts. At mid-to-late disease, animals developed fever and petechial rashes, and expressed high levels of pro-inflammatory mediators, pro-thrombotic factors, and markers indicative of liver and kidney injury. End-stage disease was characterized by shock and multi-organ failure. In summary, macaques recapitulate human SUDV disease, supporting these models for use in the development of vaccines and therapeutics.
DOI: 10.6084/m9.figshare.19984216.v2
title: Natural history of <i>Sudan ebolavirus</i> infection in rhesus and cynomolgus macaques

description: Due to its high mortality rate and continued re-emergence, Ebolavirus disease (EVD) continues to pose a serious threat to global health. A group of viruses within the genus <i>Ebolavirus</i> causes this severe hemorrhagic disease in humans: Ebola virus (EBOV; species <i>Zaire ebolavirus</i>), Sudan virus (SUDV; species <i>Sudan ebolavirus</i>), Bundibugyo virus, and Taï Forest virus. EBOV and SUDV are associated with the highest case fatality rates. While the host response to EBOV has been comprehensively examined, limited data exists for SUDV infection. For medical countermeasure testing, well-characterized SUDV nonhuman primate (NHP) models are thus needed. Here, we describe a natural history study in which rhesus (<i>N</i> = 11) and cynomolgus macaques (<i>N</i> = 14) were intramuscularly exposed to a 1000 plaque-forming unit dose of SUDV (Gulu variant). Time-course analyses of various hematological, pathological, serological, coagulation, and transcriptomic findings are reported. SUDV infection was uniformly lethal in cynomolgus macaques (100% mortality), whereas a single rhesus macaque subject (91% mortality) survived to the study endpoint (median time-to-death of ∼8.0 and ∼8.5 days in cynomolgus and rhesus macaques, respectively). Infected macaques exhibited hallmark features of human EVD. The early stage was typified by viremia, granulocytosis, lymphopenia, albuminemia, thrombocytopenia, and decreased expression of HLA-class transcripts. At mid-to-late disease, animals developed fever and petechial rashes, and expressed high levels of pro-inflammatory mediators, pro-thrombotic factors, and markers indicative of liver and kidney injury. End-stage disease was characterized by shock and multi-organ failure. In summary, macaques recapitulate human SUDV disease, supporting these models for use in the development of vaccines and therapeutics.
DOI: 10.6084/m9.figshare.20205483
title: Gut dysbacteriosis attenuates resistance to <i>Mycobacterium bovis</i> infection by decreasing cyclooxygenase 2 to inhibit endoplasmic reticulum stress

description: The role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism, by which dysbiosis affects tuberculosis, has not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to <i>Mycobacterium bovis</i> (<i>M. bovis</i>) infection. Mice are pre-treated with broad-spectrum antibiotics cocktail (Abx) to induce gut dysbiosis. Interestingly, dysbiosis of microbes showed a significant increase in the bacterial burden in the lungs and inhibited the level of COX-2. After faecal transplantation, cyclooxygenase 2 (COX-2) expression was restored and the inflammatory lesion in the lungs was reduced. Further research found that the deficiency of COX-2 inhibited endoplasmic reticulum stress (ER stress). This mechanism was completed by COX-2 interaction with BIP. Moreover, we found a positive feedback mechanism by which blocking ER stress could reduce COX-2 levels by the NF-κB pathway. Taken together, we reveal for the first time gut dysbacteriosis exacerbates <i>M. bovis</i> disease by limiting the COX-2/ER stress pathway. The finding strengthens the foundation of gut microbiota-targeted therapy for tuberculosis treatment.
DOI: 10.6084/m9.figshare.20205483.v2
title: Gut dysbacteriosis attenuates resistance to <i>Mycobacterium bovis</i> infection by decreasing cyclooxygenase 2 to inhibit endoplasmic reticulum stress

description: The role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism, by which dysbiosis affects tuberculosis, has not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to <i>Mycobacterium bovis</i> (<i>M. bovis</i>) infection. Mice are pre-treated with broad-spectrum antibiotics cocktail (Abx) to induce gut dysbiosis. Interestingly, dysbiosis of microbes showed a significant increase in the bacterial burden in the lungs and inhibited the level of COX-2. After faecal transplantation, cyclooxygenase 2 (COX-2) expression was restored and the inflammatory lesion in the lungs was reduced. Further research found that the deficiency of COX-2 inhibited endoplasmic reticulum stress (ER stress). This mechanism was completed by COX-2 interaction with BIP. Moreover, we found a positive feedback mechanism by which blocking ER stress could reduce COX-2 levels by the NF-κB pathway. Taken together, we reveal for the first time gut dysbacteriosis exacerbates <i>M. bovis</i> disease by limiting the COX-2/ER stress pathway. The finding strengthens the foundation of gut microbiota-targeted therapy for tuberculosis treatment.
DOI: 10.6084/m9.figshare.29041381
title: Co-circulation of two SARS-CoV-2 variant strains within imported pet hamsters in Hong Kong

description: During the investigation of a pet shop outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2) with probable hamster-to-human transmission, the environmental and hamster samples in epidemiologically linked pet shops were found positive for SARS-CoV-2 Delta variant AY.127 strains which are phylogenetically closely related to patients and reported European strains. This interspecies’ spill-over has triggered transmission in 58 patients epidemiologically linked to three pet shops. Incidentally, three dwarf hamsters imported from the Netherlands and centralized in a warehouse distributing animals to pet shops were positive for SARS-CoV-2 spike variant phylogenetically related to European B.1.258 strains from March 2020. This B.1.258 strain almost disappeared in July 2021. While no hamster-to-human transmission of B.1.258-like strain was found in this outbreak, molecular docking showed that its spike receptor-binding domain (RBD) has a similar binding energy to human ACE2 compared to that of Delta variant AY.127. Therefore, the potential of this B.1.258-related spike variant for interspecies jumping cannot be ignored. The co-circulation of B.1.258-related spike variants with Delta AY.127, which originated in Europe and was not previously found in Hong Kong, suggested that hamsters in our wholesale warehouse and retail pet shops more likely have acquired these viruses in the Netherlands or stopovers during delivery by aviation than locally. The risk of human-to-hamster reverse zoonosis by multiple SARS-CoV-2 variants leading to further adaptive spike mutations with subsequent transmission back to humans cannot be underestimated as an outbreak source of COVID-19. Testing imported pet animals susceptible to SARS-CoV-2 is warranted to prevent future outbreaks.
DOI: 10.6084/m9.figshare.29041381.v1
title: Co-circulation of two SARS-CoV-2 variant strains within imported pet hamsters in Hong Kong

description: During the investigation of a pet shop outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2) with probable hamster-to-human transmission, the environmental and hamster samples in epidemiologically linked pet shops were found positive for SARS-CoV-2 Delta variant AY.127 strains which are phylogenetically closely related to patients and reported European strains. This interspecies’ spill-over has triggered transmission in 58 patients epidemiologically linked to three pet shops. Incidentally, three dwarf hamsters imported from the Netherlands and centralized in a warehouse distributing animals to pet shops were positive for SARS-CoV-2 spike variant phylogenetically related to European B.1.258 strains from March 2020. This B.1.258 strain almost disappeared in July 2021. While no hamster-to-human transmission of B.1.258-like strain was found in this outbreak, molecular docking showed that its spike receptor-binding domain (RBD) has a similar binding energy to human ACE2 compared to that of Delta variant AY.127. Therefore, the potential of this B.1.258-related spike variant for interspecies jumping cannot be ignored. The co-circulation of B.1.258-related spike variants with Delta AY.127, which originated in Europe and was not previously found in Hong Kong, suggested that hamsters in our wholesale warehouse and retail pet shops more likely have acquired these viruses in the Netherlands or stopovers during delivery by aviation than locally. The risk of human-to-hamster reverse zoonosis by multiple SARS-CoV-2 variants leading to further adaptive spike mutations with subsequent transmission back to humans cannot be underestimated as an outbreak source of COVID-19. Testing imported pet animals susceptible to SARS-CoV-2 is warranted to prevent future outbreaks.
DOI: 10.6084/m9.figshare.19292094
title: Human infection with avian-origin H5N6 influenza a virus after exposure to slaughtered poultry

description: Exposure to poultry in live poultry markets is strongly associated with human infection with avian influenza virus. To effectively prevent the transmission of viruses from live poultry to humans, people have been forced to change their living habits from purchasing live poultry for consumption to purchasing freshly slaughtered poultry after the permanent closure of live poultry markets in China. In this study, we reported a case of human infection by the H5N6 virus in Hangzhou after exposure to a freshly slaughtered chicken, defying the traditional hypothesis that human infection requires a history of exposure to live poultry and indicating a novel route of infection. Rapid genomic characterization of H5N6 influenza A variants from the patient and the associated environment suggested that these viral variants were of avian origin, belonged to clade 2.3.4.4b H5 and were adapting to the human host after infection. Comparative analysis of the local H5N6 genomes showed that viral contamination in the associated environment and the poultry market was complex. Considering this case of H5N6 infection, conducting surveillance for any possible new avian influenza virus reassortment spillover to humans or other animal species is critical, and awareness of the risk of exposure to possible viral variants from infected slaughtered poultry or the associated environment must be seriously improved. <b>Highlights</b>We reported the first case of human infection with avian-origin influenza A (H5N6) virus in Zhejiang Province, southeastern China.Rapid genomic characterization of H5N6 influenza A variants from a patient and the associated environment suggested that these viral variants were of avian origin and were adapting to the human host after infection.Comparative analysis of the H5N6 genomes showed that viral contamination in the associated environment and poultry market was complex.Considering this case of H5N6 infection, the risk of exposure to possible viral variants from infected slaughtered poultry or the associated environment must be seriously considered. We reported the first case of human infection with avian-origin influenza A (H5N6) virus in Zhejiang Province, southeastern China. Rapid genomic characterization of H5N6 influenza A variants from a patient and the associated environment suggested that these viral variants were of avian origin and were adapting to the human host after infection. Comparative analysis of the H5N6 genomes showed that viral contamination in the associated environment and poultry market was complex. Considering this case of H5N6 infection, the risk of exposure to possible viral variants from infected slaughtered poultry or the associated environment must be seriously considered.
DOI: 10.6084/m9.figshare.19292094.v2
title: Human infection with avian-origin H5N6 influenza a virus after exposure to slaughtered poultry

description: Exposure to poultry in live poultry markets is strongly associated with human infection with avian influenza virus. To effectively prevent the transmission of viruses from live poultry to humans, people have been forced to change their living habits from purchasing live poultry for consumption to purchasing freshly slaughtered poultry after the permanent closure of live poultry markets in China. In this study, we reported a case of human infection by the H5N6 virus in Hangzhou after exposure to a freshly slaughtered chicken, defying the traditional hypothesis that human infection requires a history of exposure to live poultry and indicating a novel route of infection. Rapid genomic characterization of H5N6 influenza A variants from the patient and the associated environment suggested that these viral variants were of avian origin, belonged to clade 2.3.4.4b H5 and were adapting to the human host after infection. Comparative analysis of the local H5N6 genomes showed that viral contamination in the associated environment and the poultry market was complex. Considering this case of H5N6 infection, conducting surveillance for any possible new avian influenza virus reassortment spillover to humans or other animal species is critical, and awareness of the risk of exposure to possible viral variants from infected slaughtered poultry or the associated environment must be seriously improved. <b>Highlights</b>We reported the first case of human infection with avian-origin influenza A (H5N6) virus in Zhejiang Province, southeastern China.Rapid genomic characterization of H5N6 influenza A variants from a patient and the associated environment suggested that these viral variants were of avian origin and were adapting to the human host after infection.Comparative analysis of the H5N6 genomes showed that viral contamination in the associated environment and poultry market was complex.Considering this case of H5N6 infection, the risk of exposure to possible viral variants from infected slaughtered poultry or the associated environment must be seriously considered. We reported the first case of human infection with avian-origin influenza A (H5N6) virus in Zhejiang Province, southeastern China. Rapid genomic characterization of H5N6 influenza A variants from a patient and the associated environment suggested that these viral variants were of avian origin and were adapting to the human host after infection. Comparative analysis of the H5N6 genomes showed that viral contamination in the associated environment and poultry market was complex. Considering this case of H5N6 infection, the risk of exposure to possible viral variants from infected slaughtered poultry or the associated environment must be seriously considered.
DOI: 10.6084/m9.figshare.19406590
title: Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2

description: The coronavirus SARS-CoV-2 is the causative agent for the disease COVID-19. To capture the IgA, IgG, and IgM antibody response of patients infected with SARS-CoV-2 at individual epitope resolution, we constructed planar microarrays of 648 overlapping peptides that cover the four major structural proteins S(pike), N(ucleocapsid), M(embrane), and E(nvelope). The arrays were incubated with sera of 67 SARS-CoV-2 positive and 22 negative control samples. Specific responses to SARS-CoV-2 were detectable, and nine peptides were associated with a more severe course of the disease. A random forest model disclosed that antibody binding to 21 peptides, mostly localized in the S protein, was associated with higher neutralization values in cellular anti-SARS-CoV-2 assays. For antibodies addressing the N-terminus of M, or peptides close to the fusion region of S, protective effects were proven by antibody depletion and neutralization assays. The study pinpoints unusual viral binding epitopes that might be suited as vaccine candidates<b>.</b>
DOI: 10.6084/m9.figshare.19406590.v2
title: Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2

description: The coronavirus SARS-CoV-2 is the causative agent for the disease COVID-19. To capture the IgA, IgG, and IgM antibody response of patients infected with SARS-CoV-2 at individual epitope resolution, we constructed planar microarrays of 648 overlapping peptides that cover the four major structural proteins S(pike), N(ucleocapsid), M(embrane), and E(nvelope). The arrays were incubated with sera of 67 SARS-CoV-2 positive and 22 negative control samples. Specific responses to SARS-CoV-2 were detectable, and nine peptides were associated with a more severe course of the disease. A random forest model disclosed that antibody binding to 21 peptides, mostly localized in the S protein, was associated with higher neutralization values in cellular anti-SARS-CoV-2 assays. For antibodies addressing the N-terminus of M, or peptides close to the fusion region of S, protective effects were proven by antibody depletion and neutralization assays. The study pinpoints unusual viral binding epitopes that might be suited as vaccine candidates<b>.</b>
DOI: 10.6084/m9.figshare.20282244
title: Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy

description: Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg− patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg− patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg− responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy.
DOI: 10.6084/m9.figshare.20282244.v2
title: Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy

description: Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg− patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg− patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg− responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy.