Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Coronaviruses are closely monitored in the context of emerging diseases and, as illustrated with Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-coronavirus (MERS-CoV), are known to cross the species barrier and eventually to move from wildlife to humans. Knowledge of the diversity of coronaviruses in wildlife is therefore essential to better understand and prevent emergence events. This study explored the presence of coronaviruses in four wild mammal orders in France: Bats, rodents, lagomorphs, and hedgehogs. Betacoronavirus and Alphacoronavirus genera were identified. The results obtained suggest the circulation of potentially evolving virus strains, with the potential to cross the species barrier.
Understanding the pathogenesis of the SARS-CoV-2 infection is key to developing preventive and therapeutic strategies against COVID-19, in the case of severe illness but also when the disease is mild. The use of appropriate experimental animal models remains central in the in vivo exploration of the physiopathology of infection and antiviral strategies. This study describes SARS-CoV-2 intranasal infection in ferrets and hamsters with low doses of low-passage SARS-CoV-2 clinical French isolate UCN19, describing infection levels, excretion, immune responses and pathological patterns in both animal species. Individual infection with 103 p.f.u. SARS-CoV-2 induced a more severe disease in hamsters than in ferrets. Viral RNA was detected in the lungs of hamsters but not of ferrets and in the brain (olfactory bulb and/or medulla oblongata) of both species. Overall, the clinical disease remained mild, with serological responses detected from 7 days and 10 days post-inoculation in hamsters and ferrets respectively. The virus became undetectable and pathology resolved within 14 days. The kinetics and levels of infection can be used in ferrets and hamsters as experimental models for understanding the pathogenicity of SARS-CoV-2, and testing the protective effect of drugs.
The majority of bat rabies cases in Europe are attributed to European bat 1 lyssavirus (EBLV-1), circulating mainly in serotine bats (Eptesicus serotinus). Two subtypes have been defined (EBLV-1a and EBLV-1b), each associated with a different geographical distribution. In this study, we undertake a comprehensive sequence analysis based on 80 newly obtained EBLV-1 nearly complete genome sequences from nine European countries over a 45-year period to infer selection pressures, rates of nucleotide substitution, and evolutionary time scale of these two subtypes in Europe. Our results suggest that the current lineage of EBLV-1 arose in Europe ∼600 years ago and the virus has evolved at an estimated average substitution rate of ∼4.19×10−5 subs/site/year, which is among the lowest recorded for RNA viruses. In parallel, we investigate the genetic structure of French serotine bats at both the nuclear and mitochondrial level and find that they constitute a single genetic cluster. Furthermore, Mantel tests based on interindividual distances reveal the absence of correlation between genetic distances estimated between viruses and between host individuals. Taken together, this indicates that the genetic diversity observed in our E. serotinus samples does not account for EBLV-1a and -1b segregation and dispersal in Europe.
The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) sampled worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co-divergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their diverse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs sampled so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.
Understanding the pathogenesis of the SARS-CoV-2 infection is key to develop preventive and therapeutic strategies against COVID-19, in the case of severe illness but also when the disease is mild. The use of appropriate experimental animal models remains central in the in-vivo exploration of the physiopathology of infection and antiviral strategies. This study describes SARS-CoV-2 intra-nasal infection in ferrets and hamsters with low doses of low-passage SARS-CoV-2 clinical French isolate UCN19, describing infection levels, excretion, immune responses and pathological patterns in both animal species. Individual infection with 103 pfu SARS-CoV-2 induced a more severe disease in hamsters than in ferrets. Viral RNA was detected in the lungs of hamsters but not of ferrets and in the brain (olfactive and/or spinal bulbs) of both species. Overall, the clinical disease remained mild, with serological responses detected from 7 days and 10 days post inoculation in hamsters and ferrets respectively. Virus became undetectable and pathology resolved within 14 days. The kinetics and levels of infection can be used in ferrets and hamsters as experimental models for understanding the pathogenicity of SARS-CoV-2, and testing the protective effect of drugs.
Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.
Despite the considerable scientific interest in the variability and patterns of integration in the dog skull, how these patterns impact or are driven by function remains largely unexplored. Since the mandible is directly involved in mastication, it can be expected to be directly related to the development of the adductor and abductor muscles. Here, we explore whether variation in the architecture and size of the masticatory muscles is associated with the variation in mandibular shape in dogs. We obtained muscle data from the dissection of 48 dogs from different breeds and morphotypes to explore the architecture of the muscles and used 3D geometric morphometric approaches to quantify the shape of the mandible. Covariations between the masticatory muscles and mandibular shape were explored using two-block partial least square analyses (2B-PLS). Our results show there is a strong covariation between mandibular shape and masticatory muscles mass (rPLS from 0.70 to 0.74 for the first axis representing more than 90% of the total covariance) and physiological cross-sectional area (rPLS from 0.64 to 0.73 for the first axis representing more than 80% of the total covariance), irrespective of whether size is taken into account or not. These results suggest muscle size and thus attachment area requirements for individual muscles are likely drivers of mandibular shape. Moreover, mandible shape is likely to be a good predictor of muscle force. Finally, it appears that domestication of dogs has not resulted in a disuse phenotype characterized by a decoupling between form and function.
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