cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.11533008.v3
title: Contribution of Fc-dependent cell-mediated activity of a vestigial esterase-targeting antibody against H5N6 virus infection

description: The highly pathogenic avian influenza A (H5N6) virus has caused sporadic human infections with a high case fatality rate. Due to the continuous evolution of this virus subtype and its ability to transmit to humans, there is an urgent need to develop effective antiviral therapeutics. In this study, a murine monoclonal antibody 9F4 was shown to display broad binding affinity against H5Nx viruses. Furthermore, 9F4 can neutralize H5N6 pseudotyped particles and prevent entry into host cells. Additionally, ADCC/ADCP deficient L234A, L235A (LALA) and CDC deficient K322A mutants were generated and displayed comparable binding affinity and neutralizing activity as wild type 9F4 (9F4-WT). Notably, 9F4-WT, 9F4-LALA and 9F4-K322A exhibit <i>in vivo</i> protective efficacies against H5N6 infections in that they were able to reduce viral loads in mice. However, only 9F4-WT and 9F4-K322A but not 9F4-LALA were able to reduce viral pathogenesis in H5N6 challenged mice. Furthermore, depletion of phagocytic cells in mice lungs nullifies 9F4-WT's protection against H5N6 infections, suggesting a crucial role of the host's immune cells in 9F4 antiviral activity. Collectively, these findings reveal the importance of ADCC/ADCP function for 9F4-WT protection against HPAIV H5N6 and demonstrate the potential of 9F4 to confer protection against the reassortant H5-subtype HPAIVs.
DOI: 10.6084/m9.figshare.11799054.v3
title: Identification of pyrvinium pamoate as an anti-tuberculosis agent <i>in vitro</i> and <i>in vivo</i> by SOSA approach amongst known drugs

description: Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) bacteria, is a leading infectious cause of mortality worldwide. The emergence of drug-resistant <i>M. tb</i> has made control of TB more difficult. The selective optimization of side activities (SOSA) approach uses old drugs for new pharmacological targets. In the present study by using SOSA approach, we have successfully identified pyrvinium pamoate (PP) which is capable of inhibiting the growth of mycobacteria, including <i>M. tb</i> H37Rv, <i>Mycobacterium smegmatis</i>, Bacille Calmette-Guérin (BCG), <i>M. tb</i> H37Ra, and drug-resistant <i>M. tb</i> clinical isolates <i>in vitro</i> from 1280 known drugs library. The MIC<sub>99</sub> of PP, the minimum inhibitory concentration that inhibits more than 99% of <i>M. tb</i> H37Rv and the drug-resistant <i>M. tb</i> clinical isolates, ranges from 1.55 to 4.8 µg/mL. Importantly, PP could reduce the bacterial colony-forming units (CFUs) in lung, spleen and liver tissues, and effectively inhibit inflammatory response in <i>M. tb</i> H37Rv, multidrug-resistant (MDR) <i>M. tb</i> and extensively drug-resistant (XDR) <i>M.tb</i>-infected mice. Our results clearly show that the PP has the potential application for treatment of TB.
DOI: 10.6084/m9.figshare.12981337
title: Modelling <i>Toxoplasma gondii</i> infection in human cerebral organoids

description: Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of <i>in vivo</i> human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. <i>Toxoplasma gondii</i>, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited <i>in vitro</i> model systems. Here, we developed a new <i>in vitro</i> model system of <i>T. gondii</i> infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the <i>T. gondii</i> asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of <i>T. gondii</i>-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, <i>T. gondii</i> exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant <i>in vitro</i> model systems useful for advancing the understanding of <i>T. gondii</i> infections and host interactions.
DOI: 10.6084/m9.figshare.12981337.v1
title: Modelling <i>Toxoplasma gondii</i> infection in human cerebral organoids

description: Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of <i>in vivo</i> human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. <i>Toxoplasma gondii</i>, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited <i>in vitro</i> model systems. Here, we developed a new <i>in vitro</i> model system of <i>T. gondii</i> infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the <i>T. gondii</i> asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of <i>T. gondii</i>-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, <i>T. gondii</i> exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant <i>in vitro</i> model systems useful for advancing the understanding of <i>T. gondii</i> infections and host interactions.
DOI: 10.6084/m9.figshare.11799054
title: Identification of pyrvinium pamoate as an anti-tuberculosis agent <i>in vitro</i> and <i>in vivo</i> by SOSA approach amongst known drugs

description: Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) bacteria, is a leading infectious cause of mortality worldwide. The emergence of drug-resistant <i>M. tb</i> has made control of TB more difficult. The selective optimization of side activities (SOSA) approach uses old drugs for new pharmacological targets. In the present study by using SOSA approach, we have successfully identified pyrvinium pamoate (PP) which is capable of inhibiting the growth of mycobacteria, including <i>M. tb</i> H37Rv, <i>Mycobacterium smegmatis</i>, Bacille Calmette-Guérin (BCG), <i>M. tb</i> H37Ra, and drug-resistant <i>M. tb</i> clinical isolates <i>in vitro</i> from 1280 known drugs library. The MIC<sub>99</sub> of PP, the minimum inhibitory concentration that inhibits more than 99% of <i>M. tb</i> H37Rv and the drug-resistant <i>M. tb</i> clinical isolates, ranges from 1.55 to 4.8 µg/mL. Importantly, PP could reduce the bacterial colony-forming units (CFUs) in lung, spleen and liver tissues, and effectively inhibit inflammatory response in <i>M. tb</i> H37Rv, multidrug-resistant (MDR) <i>M. tb</i> and extensively drug-resistant (XDR) <i>M.tb</i>-infected mice. Our results clearly show that the PP has the potential application for treatment of TB.
DOI: 10.6084/m9.figshare.11902212
title: Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

description: The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV co-infected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive- and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.
DOI: 10.6084/m9.figshare.11902212.v3
title: Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

description: The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV co-infected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive- and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.
DOI: 10.6084/m9.figshare.12853658.v2
title: Households as hotspots of Lassa fever? Assessing the spatial distribution of Lassa virus-infected rodents in rural villages of Guinea

description: The Natal multimammate mouse (<i>Mastomys natalensis</i>) is the reservoir host of Lassa virus (LASV), an arenavirus that causes Lassa haemorrhagic fever in humans in West Africa. While previous studies suggest that spillover risk is focal within rural villages due to the spatial behaviour of the rodents, the level of clustering was never specifically assessed. Nevertheless, detailed information on the spatial distribution of infected rodents would be highly valuable to optimize LASV-control campaigns, which are limited to rodent control or interrupting human–rodent contact considering that a human vaccine is not available. Here, we analysed data from a four-year field experiment to investigate whether LASV-infected rodents cluster in households in six rural villages in Guinea. Our analyses were based on the infection status (antibody or PCR) and geolocation of rodents (<i>n </i>=<i> </i>864), and complemented with a phylogenetic analysis of LASV sequences (<i>n </i>=<i> </i>119). We observed that the majority of infected rodents were trapped in a few houses (20%) and most houses were rodent-free at a specific point in time (60%). We also found that LASV strains circulating in a specific village were polyphyletic with respect to neighbouring villages, although most strains grouped together at the sub-village level and persisted over time. In conclusion, our results suggest that: (i) LASV spillover risk is heterogeneously distributed within villages in Guinea; (ii) viral elimination in one particular village is unlikely if rodents are not controlled in neighbouring villages. Such spatial information should be incorporated into eco-epidemiological models that assess the cost-efficiency of LASV control strategies.
DOI: 10.6084/m9.figshare.13313282
title: Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

description: Due to the advanced stage of polio eradication, the possible role of non-polio enteroviruses (NPEVs) associated to acute flaccid paralysis (AFP) cases has been highlighted. In this study, we described epidemiological aspects of NPEVs infections associated to AFP and explore the viral genetic diversity, information still scarce in Brazil. From 2005 to 2017, 6707 stool samples were collected in the scope of the Brazilian Poliomyelitis Surveillance Program. NPEVs were isolated in 359 samples (5.3%) and 341 (94.9%) were genotyped. About 46 different NPEV types were identified with the following detection pattern EV-B &gt; EV-A &gt; EV-C. The major EV-types were CVA2, CV4, EV-A71, CVB3, CVB5, E6, E7, E11, CVA13 and EV-C99, which corresponds to 51.6% of the total. Uncommon types, such as CVA12, EV-90 and CVA11, were also identified. Different E6 genogroups were observed, prevailing the GenIII, despite periods of co-circulation, and replacement of genogroups along time. CVA2 sequences were classified as genotype C and data suggested its dispersion in South-American countries. CVA13 viruses belonged to cluster B and Venezuelan viruses composed a new putative cluster. This study provides extensive information on enterovirus diversity associated with AFP, reinforcing the need of tailoring current surveillance strategies to timely monitor emergence/re-emergence of NPEVs.
DOI: 10.6084/m9.figshare.13313282.v1
title: Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

description: Due to the advanced stage of polio eradication, the possible role of non-polio enteroviruses (NPEVs) associated to acute flaccid paralysis (AFP) cases has been highlighted. In this study, we described epidemiological aspects of NPEVs infections associated to AFP and explore the viral genetic diversity, information still scarce in Brazil. From 2005 to 2017, 6707 stool samples were collected in the scope of the Brazilian Poliomyelitis Surveillance Program. NPEVs were isolated in 359 samples (5.3%) and 341 (94.9%) were genotyped. About 46 different NPEV types were identified with the following detection pattern EV-B &gt; EV-A &gt; EV-C. The major EV-types were CVA2, CV4, EV-A71, CVB3, CVB5, E6, E7, E11, CVA13 and EV-C99, which corresponds to 51.6% of the total. Uncommon types, such as CVA12, EV-90 and CVA11, were also identified. Different E6 genogroups were observed, prevailing the GenIII, despite periods of co-circulation, and replacement of genogroups along time. CVA2 sequences were classified as genotype C and data suggested its dispersion in South-American countries. CVA13 viruses belonged to cluster B and Venezuelan viruses composed a new putative cluster. This study provides extensive information on enterovirus diversity associated with AFP, reinforcing the need of tailoring current surveillance strategies to timely monitor emergence/re-emergence of NPEVs.
DOI: 10.6084/m9.figshare.12011181
title: Tropism, pathology, and transmission of equine parvovirus-hepatitis

description: Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and <i>in situ</i> hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.
DOI: 10.6084/m9.figshare.12011181.v3
title: Tropism, pathology, and transmission of equine parvovirus-hepatitis

description: Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and <i>in situ</i> hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.
DOI: 10.6084/m9.figshare.13360566
title: Low incidence of airborne SARS-CoV-2 in acute care hospital rooms with optimized ventilation

description: The worldwide repercussions of COVID-19 sparked important research efforts, yet the detailed contribution of aerosols in the transmission of SARS-CoV-2 has not been elucidated. In an attempt to quantify viral aerosols in the environment of infected patients, we collected 100 air samples in acute care hospital rooms hosting 22 patients over the course of nearly two months using three different air sampling protocols. Quantification by RT-qPCR (ORF1b) led to 11 positive samples from 6 patient rooms (<i>C<sub>t</sub></i> &lt; 40). Viral cultures were negative. No correlation was observed between particular symptoms, length of hospital stay, clinical parameters, and time since symptom onset and the detection of airborne viral RNA. Low detection rates in the hospital rooms may be attributable to the appropriate application of mitigation methods according to the risk control hierarchy, such as increased ventilation to 4.85 air changes per hour to create negative pressure rooms. Our work estimates the mean emission rate of patients and potential airborne concentration in the absence of ventilation. Additional research is needed understand aerosolization events occur, contributing factors, and how best to prevent them.
DOI: 10.6084/m9.figshare.11902212.v2
title: Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

description: The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV co-infected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive- and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.
DOI: 10.6084/m9.figshare.13360566.v1
title: Low incidence of airborne SARS-CoV-2 in acute care hospital rooms with optimized ventilation

description: The worldwide repercussions of COVID-19 sparked important research efforts, yet the detailed contribution of aerosols in the transmission of SARS-CoV-2 has not been elucidated. In an attempt to quantify viral aerosols in the environment of infected patients, we collected 100 air samples in acute care hospital rooms hosting 22 patients over the course of nearly two months using three different air sampling protocols. Quantification by RT-qPCR (ORF1b) led to 11 positive samples from 6 patient rooms (<i>C<sub>t</sub></i> &lt; 40). Viral cultures were negative. No correlation was observed between particular symptoms, length of hospital stay, clinical parameters, and time since symptom onset and the detection of airborne viral RNA. Low detection rates in the hospital rooms may be attributable to the appropriate application of mitigation methods according to the risk control hierarchy, such as increased ventilation to 4.85 air changes per hour to create negative pressure rooms. Our work estimates the mean emission rate of patients and potential airborne concentration in the absence of ventilation. Additional research is needed understand aerosolization events occur, contributing factors, and how best to prevent them.