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[en] Highlights: • Clinical isolates of HCoV-OC43 and -HKU1 were isolated from ALI-cultured HBTE cells. • Clinical isolates of HCoVs preferred the TMRRSS2 to cathepsins for cell entry. • Cell culture adapted HCoV-OC43 lost the ability to replicate in HBTE-ALI culture. Human coronaviruses (HCoVs) enter cells via two distinct pathways: the endosomal pathway using cathepsins to activate spike protein and the cell-surface or early endosome pathway using extracellular proteases such as transmembrane protease serine 2 (TMPRSS2). We previously reported that clinical isolates of HCoV-229E preferred cell-surface TMPRSS2 to endosomal cathepsin for cell entry, and that they acquired the ability to use cathepsin L by repeated passage in cultured cells and were then able to enter cells via the endosomal pathway. Here, we show that clinical isolates of HCoV-OC43 and -HKU1 preferred the cell-surface TMRRSS2 to endosomal cathepsins for cell entry, similar to HCoV-229E. In addition, the cell-culture-adapted HCoV-OC43 lost the ability to infect and replicate in air-liquid interface cultures of human bronchial tracheal epithelial cells. These results suggest that circulating HCoVs in the field generally use cell-surface TMPRSS2 for cell entry, not endosomal cathepsins, in human airway epithelial cells.
[en] Low radiation doses targeted at pulmonary lesions in case of patients suffering from severe Covid-19, have shown their interest to stop tissues damage and favour healing. It seems that irradiation resets macrophages (cells that can absorb pathogens) to give them a more anti-inflammatory role. (A.C.)
[en] Transcriptomics has the potential to discover new RNA virus genomes by sequencing total intracellular RNA pools. In this study, we have searched publicly available transcriptomes for sequences similar to viruses of the Nidovirales order. We report two potential nidovirus genomes, a highly divergent 35.9 kb likely complete genome from the California sea hare Aplysia californica, which we assign to a nidovirus named Aplysia abyssovirus 1 (AAbV), and a coronavirus-like 22.3 kb partial genome from the ornamented pygmy frog Microhyla fissipes, which we assign to a nidovirus named Microhyla alphaletovirus 1 (MLeV). AAbV was shown to encode a functional main proteinase, and a translational readthrough signal. Phylogenetic analysis suggested that AAbV represents a new family, proposed here as Abyssoviridae. MLeV represents a sister group to the other known coronaviruses. The importance of MLeV and AAbV for understanding nidovirus evolution, and the origin of terrestrial nidoviruses are discussed.
[en] We hope that the suggestions for conducting IAEA nutrition studies during the COVID-19 pandemic that we have put together in response to related questions from project counterparts will be useful. The newsletter also includes reflections from a researcher at our Collaborating Centre in Bangalore, India, on stalled research activities due to COVID-19. Don’t miss the UNSCN contribution on the impact of COVID-19 on food systems and food environments including useful links to available resources. Check also the news on our other activities, new publications and success stories
[en] Highlights: • We provide a historical perspective on the identification of coronavirus (CoV) nsp15 as an endoribonuclease (EndoU). • We review the structural and functional studies of the enzymatic properties of EndoU. • We describe studies that found a non-essential role of EndoU activity in CoV replication in immortalized fibroblast cells. • We describe the discovery that EndoU is essential in evasion of host antiviral defenses in macrophages and in vivo. Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.
[en] Highlights: • Nidoviruses display differences in sensitivity towards cyclophilin A depletion. • Replication of MERS-coronavirus is reduced modestly in cyclophilin A-knockout cells. • Equine arteritis virus replication is strongly inhibited by cyclophilin A depletion. • Chromosomal anomalies complicate CRISPR/Cas9-mediated gene editing in Huh7 cells. Cyclophilin A (CypA) is an important host factor in the replication of a variety of RNA viruses. Also the replication of several nidoviruses was reported to depend on CypA, although possibly not to the same extent. These prior studies are difficult to compare, since different nidoviruses, cell lines and experimental set-ups were used. Here, we investigated the CypA dependence of three distantly related nidoviruses that can all replicate in Huh7 cells: the arterivirus equine arteritis virus (EAV), the alphacoronavirus human coronavirus 229E (HCoV-229E), and the betacoronavirus Middle East respiratory syndrome coronavirus (MERS-CoV). The replication of these viruses was compared in the same parental Huh7 cells and in CypA-knockout Huh7 cells generated using CRISPR/Cas9-technology. CypA depletion reduced EAV yields by ~ 3-log, whereas MERS-CoV progeny titers were modestly reduced (3-fold) and HCoV-229E replication was unchanged. This study reveals that the replication of nidoviruses can differ strikingly in its dependence on cellular CypA.
[en] The measures implemented to limit the spread of Covid-19 have brought many challenges on the work organization, the radiation protection being no exception. The IRPA Young Generation Network has investigated through a collection of testimonies the impacts of these measures and how the continuity and consistency of radiation protection was ensured. This article presents the results of the analysis of the testimonies. The impacts of the Covid-19 for each of the radiation protection related sectors covered by the survey are presented from a young generation perspective. The impacts are never negligible and even more important in some sectors and for some type of work. The adaptations made to the radiation protection and how they were implemented are shown, as well as the lessons-learned from these unprecedented circumstances. (authors)
[en] iVetNet is an information platform run and maintained by the IAEA, in full cooperation with the Food and Agriculture Organization of the United Nations (FAO), for compiling, disseminating and harmonizing techniques for the detection and characterization of transboundary animal and zoonotic pathogens. Through the sharing of disease detection procedures, results where applicable and other technical data, the platform aims to support responses by the FAO and the World Organisation for Animal Health to animal and zoonotic disease outbreaks. Launching in 2021, iVetNet will bring together over 1000 laboratories across the globe and offer its users access to information and validated and verified procedures for the detection and characterization of animal and zoonotic pathogens, such as foot-and-mouth disease, African swine fever, lumpy skin disease, Ebola, Zika, COVID-19 and others.
[en] Aircraft produce condensation trails, which are thought to increase high-level cloudiness under certain conditions. However the magnitude of such an effect and whether this contributes substantially to the radiative forcing due to the aviation sector remain uncertain. The very substantial, near-global reduction in air traffic in response to the COVID-19 outbreak offers an unprecedented opportunity to identify the anthropogenic contribution to the observed cirrus coverage and thickness. Here we show, using an analysis of satellite observations for the period March–May 2020, that in the 20% of the Northern Hemisphere mid-latitudes with the largest air traffic reduction, cirrus fraction was reduced by ∼9 ± 1.5% on average, and cirrus emissivity was reduced by ∼2 ± 5% relative to what they should have been with normal air traffic. The changes are corroborated by a consistent estimate based on linear trends over the period 2011–2019. The change in cirrus translates to a global radiative forcing of 61 ± 39 mW m−2. This estimate is somewhat smaller than previous assessments. (letter)
[en] Highlights: • A SARS-CoV sister clade member, Betacoronavirus EPI1, found in Western Europe. • Betacoronavirus EPI1 circulates in Rhinolophus ferrumequinum bat in Western Europe. • 9 alphacoronaviruses species found in Vespertillionidae and Miniopteridae bats. • Rhinolophus ferrumequinum hosts Betacov EPI1 and Alphacov EPI4, EPI6 and EPI7. • Alphacoronavirus EPI6 is strictly associated with Rhinolophus ferrumequinum. The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus ferrumequinum were identified. The diversity and prevalence of bat coronaviruses presently reported from western Europe is much higher than previously described and includes a SARS-CoV sister group. This diversity demonstrates the dynamic evolution and circulation of coronaviruses in this species. That said, the identified coronaviruses were consistently associated with a particular bat species or genus, and these relationships were maintained no matter the geographic location. The observed phylogenetic grouping of coronaviruses from the same species in Europe and Asia, emphasizes the role of host/pathogen coevolution in this group.