Infectious viruses so precisely fit their hosts that the study of natural viral infection depends on host-specific mechanisms that affect viral infection. For human parainfluenza virus 3, a prevalent ...cause of lower respiratory tract disease in infants, circulating human viruses are genetically different from viruses grown in standard laboratory conditions; the surface glycoproteins that mediate host cell entry on circulating viruses are suited to the environment of the human lung and differ from those of viruses grown in cultured cells. Polarized human airway epithelium cultures have been used to represent the large, proximal airways of mature adult airways. Here we modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids derived from human pluripotent stem cells contain mesoderm and pulmonary endoderm and develop into branching airway and alveolar structures. Whole-genome sequencing analysis of parainfluenza viruses replicating in the organoids showed maintenance of nucleotide identity, suggesting that no selective pressure is exerted on the virus in this tissue. Infection with parainfluenza virus led to viral shedding without morphological changes, while respiratory syncytial virus infection induced detachment and shedding of infected cells into the lung organoid lumens, reminiscent of parainfluenza and respiratory syncytial virus in human infant lungs. Measles virus infection, in contrast, induced syncytium formation. These human stem cell-derived lung organoids may serve as an authentic model for respiratory viral pathogenesis in the developing or infant lung, recapitulating respiratory viral infection in the host.
Respiratory viruses are among the first pathogens encountered by young children, and the significant impact of these viral infections on the developing lung is poorly understood. Circulating viruses are suited to the environment of the human lung and are different from those of viruses grown in cultured cells. We modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids, derived from human pluripotent stem cells, develop into branching airway and alveolar structures and provide a tissue environment that maintains the authentic viral genome. The lung organoids can be genetically engineered prior to differentiation, thereby generating tissues bearing or lacking specific features that may be relevant to viral infection, a feature that may have utility for the study of host-pathogen interaction for a range of lung pathogens.
Building a global immune system Lipkin, W. I.; Briese, T.
Human vaccines & immunotherapeutics,
11/2022, Letnik:
18, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The COVID-19 pandemic exposed global vulnerabilities to emerging infectious diseases, heralded by earlier outbreaks, that did not result in appropriate investments in surveillance, international ...collaboration, and response. We propose specific steps that should be taken to reduce future risks to public health, economic and political stability, and food security.
In 1983, reports of antibodies in subjects with major depressive disorder (MDD) to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to molecular ...cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV). This advance has enabled the development of new diagnostic assays, including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990, more than 80 studies have reported an association between BDV and a wide range of human illnesses that include MDD, bipolar disorder (BD), schizophrenia (SZ), anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme. However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serological and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 SZ/control pairs, 66 BD/control pairs and 80 MDD/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders.
Introduction
The object of this study was to evaluate the primary stability of tibial interference screw (IFS) fixation in single-stage revision surgery of the anterior cruciate ligament (ACL) in the ...case of recurrent instability after ACL repair with dynamic intraligamentary stabilization (DIS), dependent on the implant position during DIS.
Materials and methods
Tibial aperture fixation in ACL reconstruction (ACL-R) was performed in a porcine knee model using an IFS. Native ACL-R was performed in the control group (
n
= 15). In the intervention groups DIS and subsequent implant removal were performed prior to single-stage revision ACL-R. A distance of 20 mm in group R-DIS1 (
n
= 15) and 5 mm in group R-DIS2 (
n
= 15) was left between the joint line and the implant during DIS. Specimens were mounted in a material-testing machine and load-to-failure was applied in a worst-case-scenario.
Results
Load to failure was 454 ± 111 N in the R-DIS1 group, 154 ± 71 N in the R-DIS2 group and 405 ± 105 N in the primary ACL-R group. Load-to-failure, stiffness and elongation of the group R-DIS2 were significantly inferior in comparison to R-DIS1 and ACL-R respectively (
p
< 0.001). No significant difference was found between load-to-failure, stiffness and elongation of R-DIS1 and the control group.
Conclusion
Primary stability of tibial aperture fixation in single-stage revision ACL-R in case of recurrent instability after DIS depends on monobloc position during ACL repair. Primary stability is comparable to aperture fixation in primary ACL-R, if a bone stock of 20 mm is left between the monobloc and the tibial joint line during the initial procedure.
Aims/hypothesis
Viruses are candidate causative agents in the pathogenesis of autoimmune (type 1) diabetes. We hypothesised that children with a rapid onset of type 1 diabetes may have been exposed ...to such agents shortly before the initiation of islet autoimmunity, possibly at high dose, and thus study of these children could help identify viruses involved in the development of autoimmune diabetes.
Methods
We used next-generation sequencing to search for viruses in plasma samples and examined the history of infection and fever in children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study who progressed to type 1 diabetes within 6 months from the appearance of islet autoimmunity, and in matched islet-autoantibody-negative controls.
Results
Viruses were not detected more frequently in plasma from rapid-onset patients than in controls during the period surrounding seroconversion. In addition, infection histories were found to be similar between children with rapid-onset diabetes and control children, although episodes of fever were reported less frequently in children with rapid-onset diabetes.
Conclusions/interpretation
These findings do not support the presence of viraemia around the time of seroconversion in young children with rapid-onset type 1 diabetes.
1. Hypericum perforatum, St John's wort, is an invasive weed of natural and agroecosystems in south-eastern Australia. In previous work we used a long-term data set to determine which plant traits ...and environmental factors influence population growth and persistence in this species. These results were then used to parameterize an individual-based model of the population dynamics of H. perforatum, and this model was used to make predictions about what control strategies will be most effective for populations in open and shaded sites. 2. The model was constructed using multi-level, mixed-effects statistical models of growth, survival, fecundity and damage, incorporating intrinsic plant variables, environmental variables, herbivory and spatial and temporal stochasticity. 3. We found that populations in shaded and open sites had different dynamics and responses to control strategies. Shaded populations took longer to reach infestation densities and were less affected by herbivory and reductions in survival than open populations. Open populations increased faster in response to increases in rainfall, but this was not so for shaded populations. 4. We used sensitivity testing and management simulations to predict that the most successful control strategies will involve a reduction in vegetative size in both open and shaded sites. Reductions in flowering stem size and survival in shaded and open sites, respectively, are predicted to be the next most successful strategies. Dry conditions in the austral autumn/winter adversely affect populations in both open and shaded sites. 5. Synthesis and applications. These models have enabled us to rank management strategies based on quantitative analysis of their potential effects on population size. This is an important tool not only for ecologists concerned with control of invasive species but for conservation biologists trying to understand the factors limiting a rare or endangered species.
1. Hypericum perforatum, St John's wort, is an invasive perennial herb that is especially problematic on waste ground, roadsides, pastures and open woodland in south-eastern Australia. We use ...detailed data from a long-term observational study to develop quantitative models of the factors affecting growth, survival and fecundity of H. perforatum individuals. 2. Multi-level or hierarchical mixed-effects statistical models are used to analyse how environmental and intrinsic plant variables affect growth and reproduction within a complex nested spatial and temporal context. These techniques are relatively underused in ecology, despite the prevalence of multi-level and repeated-measures data generated from ecological studies. 3. We found that plant size (rosette or flowering stems) was strongly correlated with all life stages studied (growth, probability of flowering, asexual reproduction, survival and fruit production). Environmental variables such as herbivory, ground cover and rainfall had significant effects on several life stages. 4. Significant spatial variation at the quadrat level was found in the probability of flowering, flowering stem growth and fruit production models; variation at all other spatial levels in all models was non-significant. Yearly temporal variation was significant in all models where multi-year data were available. 5. Plants in shaded habitats were smaller but had higher survival probabilities than plants in open habitats. They are therefore likely to have slightly different population dynamics. 6. Synthesis and applications. Analysis of these models for H. perforatum has provided insights into which plant traits and environmental factors determine how populations increase and persist in exotic ecosystems, enabling population management strategies to be most effectively targeted. Spatially and temporally correlated data are often collected in long-term ecological studies and multi-level models are a way in which we can fully exploit the wealth of data available. Without these tools data are either under-exploited or crucial assumptions of independence on which many statistics are based are contravened.
Recently, we identified Batai virus as the M-segment reassortment partner of Ngari virus. Extension of genetic analyses to other orthobunyaviruses related to the Bunyamwera serogroup indicates ...additional natural genome reassortments. Whereas the relative phylogenetic positions of all three genome segment sequences were similar for Northway and Kairi viruses, the relative positions of Potosi and Main Drain virus M-segment sequences diverged from those of their S- and L-segments. Our findings indicate M-segment reassortment in Potosi and Main Drain viruses and demonstrate natural genome reassortment as a driving force in the evolution of viruses of the Bunyamwera serogroup.
Merino Walk virus (MWV), a proposed novel tentative species of the family Arenaviridae, was isolated from a rodent, Myotomys unisulcatus, collected at Merino Walk, Eastern Cape, South Africa, in ...1985. Full-length genomic sequence confirmed MWV as an arenavirus related distantly to Mobala, Mopeia and Ippy viruses, all members of the Old World arenavirus complex. We propose MWV as a tentative novel species in the Lassa-lymphocytic choriomeningitis virus complex, based on its isolation from a novel rodent species and its genetic and serological characteristics.
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