Mpox: A case study for a one health approach to infectious disease prevention

Mpox has been declared a global health emergency twice by the World Health Organization due to its impacts within and beyond Africa. Enzootic in Central and West African wildlife, mpox outbreaks have resulted from zoonotic spillover, with recent events revealing increased human-to-human transmission. Factors like population growth and environmental disruption, alongside reduced smallpox immunity, increase emergence risk. In addition, the emergence in South Kivu of a distinct subclade of mpox virus points at a currently understudied aspect of mpox virus lineages and their dynamics in reservoir hosts. A One Health approach—integrating human, animal, and environmental science—is essential for reducing the risk of mpox emergence. This approach should encompass ecological studies to understand putative reservoir population dynamics and the potential for interventions, reducing activities that increase human-animal contacts, respectful community engagement to reduce spillover risk from cultural practices (such as hunting multiple species of wildlife for consumption), and socially acceptable and equitable access to medical and non-medical countermeasures to prevent or control ongoing human-to-human transmission. Politically supported collaborative efforts across disciplines with involvement of stakeholders are critical to promote and strengthen socially and environmentally sustainable practices to mitigate future outbreaks

Mpox: A case study for a one health approach to infectious disease prevention

Mpox has been declared a global health emergency twice by the World Health Organization due to its impacts within and beyond Africa. Enzootic in Central and West African wildlife, mpox outbreaks have resulted from zoonotic spillover, with recent events revealing increased human-to-human transmission. Factors like population growth and environmental disruption, alongside reduced smallpox immunity, increase emergence risk. In addition, the emergence in South Kivu of a distinct subclade of mpox virus points at a currently understudied aspect of mpox virus lineages and their dynamics in reservoir hosts. A One Health approach—integrating human, animal, and environmental science—is essential for reducing the risk of mpox emergence. This approach should encompass ecological studies to understand putative reservoir population dynamics and the potential for interventions, reducing activities that increase human-animal contacts, respectful community engagement to reduce spillover risk from cultural practices (such as hunting multiple species of wildlife for consumption), and socially acceptable and equitable access to medical and non-medical countermeasures to prevent or control ongoing human-to-human transmission. Politically supported collaborative efforts across disciplines with involvement of stakeholders are critical to promote and strengthen socially and environmentally sustainable practices to mitigate future outbreaks.fals

The prefusion structure of herpes simplex virus glycoprotein B.

Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins

Strict Biosecurity and Epidemiological Segmentation Enable Partial Culling During a Highly Pathogenic Avian Influenza Outbreak

Martin J Oettler,1,* Gerald Stumpf,2,* Katja Schulz,1 Matthias Todte,3 Klim Hüttner,4 Heidemarie Heyne,5 Thomas C Mettenleiter,6 Franz J Conraths,1 Carola Sauter-Louis1 1Institute of Epidemiology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, 17493, Germany; 2Veterinary and Food Inspection Office, Güstrow, 18273, Germany; 3Veterinary Practice MMT, Köthen (Anhalt) 06366, Germany; 4Veterinary Epidemiological Service, State Institute for Agriculture, Food Safety and Fisheries Mecklenburg-Western Pomerania, Rostock, 18059, Germany; 5Animal Health Division, Ministry for Climate Protection, Agriculture, Rural Areas and the Environment of Mecklenburg-Western Pomerania, Schwerin, 19061, Germany; 6Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, 17493, Germany*These authors contributed equally to this workCorrespondence: Martin J Oettler, Institute of Epidemiology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, Greifswald-Insel Riems, 17493, Germany, Email [email protected]: The mandatory procedures to be followed after official confirmation of an outbreak of category A animal infectious diseases, including highly pathogenic avian influenza (HPAI), is laid down in European and national legislation. Typically, an outbreak of HPAI results in the destruction of the entire poultry population on the affected holding.Case Presentation: The presented case reports a deviation from this approach, demonstrating the practicality of partial culling in a highly biosecure, epidemiologically segmented holding. These on-site circumstances together with the specific risk assessment led to the elimination of only the affected unit, thereby inhibiting the further spread of the disease. After the destruction of the respective unit (farm), the other farms were closely monitored and tested continuously negative for HPAI virus (HPAIV) despite intensive systematic sampling. In the end, this procedure saved approximately 138,000 animals, ie 75% of the poultry population of the holding from destruction.Conclusion: This case demonstrates the effectiveness of proper management and high-level biosecurity to avoid excessive destruction of animals in case of an infectious disease outbreak. It might be suitable as a best-practice example in similar situations.Keywords: epidemiology, epidemiological unit, biosafety, infectious animal diseases, poultr

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid-Tegument Complexes along Microtubules

Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A–ORF45 interaction either by the use of a headless dominant negative (DN) mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles

Virally and physically transgenized equine adipose-derived stromal cells as a cargo for paracrine secreted factors

<p>Abstract</p> <p>Background</p> <p>Adipose-Derived Stromal Cells have been shown to have multiple lineage differentiation properties and to be suitable for tissues regeneration in many degenerative processes. Their use has been proposed for the therapy of joint diseases and tendon injuries in the horse. In the present report the genetic manipulation of Equine Adipose-Derived Stromal Cells has been investigated.</p> <p>Results</p> <p>Equine Adipose-Derived Stromal Cells were successfully virally transduced as well as transiently and stably transfected with appropriate parameters, without detrimental effect on their differentiation properties. Moreover, green fluorescent protein alone, fused to <it>neo </it>gene, or co-expressed as bi-cistronic reporter constructs, driven by viral and house-keeping gene promoters, were tested. The better expressed cassette was employed to stably transfect Adipose-Derived Stromal Cells for cell therapy purposes. Stably transfected Equine Adipose-Derived Stromal Cells with a heterologous secreted viral antigen were able to immunize horses upon injection into the lateral wall of the neck.</p> <p>Conclusion</p> <p>This study provides the methods to successfully transgenize Adipose-Derived Stromal Cells both by lentiviral vector and by transfection using optimized constructs with suitable promoters and reporter genes. In conclusion these findings provide a working platform for the delivery of potentially therapeutic proteins to the site of cells injection via transgenized Equine Adipose-Derived Stromal Cells.</p

One Health: A new definition for a sustainable and healthy future

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Targeting of Pseudorabies Virus Structural Proteins to Axons Requires Association of the Viral Us9 Protein with Lipid Rafts

The pseudorabies virus (PRV) Us9 protein plays a central role in targeting viral capsids and glycoproteins to axons of dissociated sympathetic neurons. As a result, Us9 null mutants are defective in anterograde transmission of infection in vivo. However, it is unclear how Us9 promotes axonal sorting of so many viral proteins. It is known that the glycoproteins gB, gC, gD and gE are associated with lipid raft microdomains on the surface of infected swine kidney cells and monocytes, and are directed into the axon in a Us9-dependent manner. In this report, we determined that Us9 is associated with lipid rafts, and that this association is critical to Us9-mediated sorting of viral structural proteins. We used infected non-polarized and polarized PC12 cells, a rat pheochromocytoma cell line that acquires many of the characteristics of sympathetic neurons in the presence of nerve growth factor (NGF). In these cells, Us9 is highly enriched in detergent-resistant membranes (DRMs). Moreover, reducing the affinity of Us9 for lipid rafts inhibited anterograde transmission of infection from sympathetic neurons to epithelial cells in vitro. We conclude that association of Us9 with lipid rafts is key for efficient targeting of structural proteins to axons and, as a consequence, for directional spread of PRV from pre-synaptic to post-synaptic neurons and cells of the mammalian nervous system

Prevention of zoonotic spillover: From relying on response to reducing the risk at source.

The devastating impact of Coronavirus Disease 2019 (COVID-19) on human health globally has prompted extensive discussions on how to better prepare for and safeguard against the next pandemic. Zoonotic spillover of pathogens from animals to humans is recognized as the predominant cause of emerging infectious diseases and as the primary cause of recent pandemics [1]. This spillover risk is increased by a range of factors (called drivers) that impact the nature, frequency, and intensity of contact between humans and wild animals. Many of these drivers are related to human impact, for example, deforestation and changes in land use and agricultural practices. While it is clear that the triad of prevention-preparedness-response (P-P-R) is highly relevant, there is much discussion on which of these 3 strategic activities in the field of emerging infectious disease should be prioritized and how to optimally target resources. For this, it is important to understand the scope of the respective activity and the consequences of prioritization.fals