The infectious bursal disease virus (IBDV) is the archetypal member of the Birnaviridae family and the etiological agent of Gumboro disease, a highly contagious immunosuppressive infection of concern to the global poultry sector for its adverse health effects in chicks. Unlike most double-stranded RNA (dsRNA) viruses, that enclose their genomes within specialized cores throughout their viral replication cycle, birnaviruses organize their bisegmented dsRNA genome in ribonucleoproteins (RNPs) structures. Recently, we demonstrated that IBDV exploits endosomal membranes for replication. The establishment of IBDV replication machinery on the cytosolic leaflet of endosomal compartments is mediated by the viral protein VP3 and its intrinsic ability to target endosomes. In this study, we identified the early endosomal Phosphatidylinositol 3- phosphate [PtdIns(3)P] as a key host factor of VP3 association with endosomal membranes and consequent establishment of IBDV replication complexes in early endosomes. Indeed, our data reveal a crucial role for PtdIns(3)P in IBDV replication. Overall, our findings provide new insights into the replicative strategy of birnaviruses and strongly suggest that it resembles those of positive-strand RNA (+ssRNA) viruses, which replicates in association with host membranes. Furthermore, our findings support the role of birnaviruses as evolutionary intermediaries between +ssRNA and dsRNA viruses, and importantly, demonstrate a novel role for PtdIns(3)P in the replication of a dsRNA virus. IMPORTANCE The infectious bursal disease virus (IBDV) infects chicks and is the causative agent of Gumboro disease. During IBDV outbreaks in recent decades, the emergence of very virulent variants and the lack of effective prevention/treatment strategies to fight this disease have had devastating consequences on the poultry industry. IBDV belongs to the peculiar Birnaviridae family. Unlike most dsRNA viruses, birnaviruses organize their genomes in ribonucleoprotein complexes and replicate in a core-independent manner. We have recently demonstrated that IBDV exploits host-cell endosomes as platforms for viral replication, a process that depends on the VP3 viral protein. In this study, we delved deeper into the molecular characterization of IBDV-endosomes association and investigated the role of host-cell phosphatidylinositides lipids in VP3 protein localization and IBDV infection. Together our findings demonstrate that PtdIns(3)P serves as a scaffold for the association of VP3 to endosomes and reveal its essential role for IBDV replication.
Wearable technology and live video conferencing: The development of an affordable virtual teaching platform to enhance clinical skills education during the COVID-19 pandemic Technologie portable et vidéoconférence en direct : élaboration d'une plateforme d'enseignement virtuel abordable pour améliorer l'enseignement des habiletés cliniques pendant la pandémie de la COVID-19
Purpose: Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the incidence and progression of GA after intravitreal injections of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration. Methods: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to May 2020. Included studies reported on the progression or development of GA in eyes with neovascular age-related macular degeneration after antivascular endothelial growth factor therapy. Results: Thirty-one articles and 4,609 study eyes (4,501 patients) were included. Eyes received a mean of 17.7 injections over 35.2 months. The prevalence of GA at baseline was 9.7%. The pooled incidence of GA was 30.5% at the end of follow-up. There was a positive, moderate linear correlation between the mean total number of injections and GA incidence at the final follow-up (R2 = 0.30; P = 0.01). Monthly treatment was associated with a significantly higher risk for GA development relative to pro re nata (relative risk = 1.40, 95% confidence interval = [1.21–1.61], P < 0.001). Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen. Conclusion: We found an association between the frequency and number of treatments with antivascular endothelial growth factor agents and the development of GA in neovascular age-related macular degeneration. Future studies should clarify risk factors, population characteristics, and relative contributions of treatment and disease progression on GA development in this context.
Implication Statement We piloted a virtual teaching tool comprised of a chest-mounted smartphone streaming point-of-view footage over videoconferencing software to deliver a physical exam skills session. Compared to medical students taught via third person view through pre-recorded video followed by preceptor-led discussion, a higher proportion of students taught via point-of-view wearable technology reported improved knowledge of demonstrated skills and feeling engaged, comfortable interacting with their tutor, and better able to visualize demonstrated exam maneuvers. This accessible, affordable, and easily replicable innovation can potentially enhance virtual clinical skills teaching and enable novel distant clinical learning opportunities for healthcare professions students and educators.
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