Constant surveillance of live poultry markets (LPMs) is currently the best way to predict and identify emerging avian influenza viruses (AIVs) that pose a potential threat to public health. Through surveillance of LPMs from 16 provinces and municipalities in China during 2014-2016, we identified 3,174 AIV-positive samples and isolated and sequenced 1,135 AIVs covering 31 subtypes. Our analysis shows that H5N6 has replaced H5N1 as one of the dominant AIV subtypes in southern China, especially in ducks. Phylogenetic analysis reveals that H5N6 arose from reassortments of H5 and H6N6 viruses, with the hemagglutinin and neuraminidase combinations being strongly lineage specific. H5N6 viruses constitute at least 34 distinct genotypes derived from various evolutionary pathways. Notably, genotype G1.2 virus, with internal genes from the chicken H9N2/H7N9 gene pool, was responsible for at least five human H5N6 infections. Our findings highlight H5N6 AIVs as potential threats to public health and agriculture.

COVID-19, caused by SARS-CoV-2, has resulted in severe and unprecedented economic and social disruptions in the world. Nucleocapsid (N) protein, which is the major structural component of the virion and is involved in viral replication, assembly and immune regulation, plays key roles in the viral life cycle. Here, we solved the crystal structures of the N-and C-terminal domains (N-NTD and N-CTD) of SARS-CoV-2 N protein, at 1.8 and 1.5 Å resolution, respectively. Both structures show conserved features from other CoV N proteins. The binding sites targeted by small molecules against HCoV-OC43 and MERS-CoV, which inhibit viral infection by blocking the RNA-binding activity or normal oligomerization of N protein, are relatively conserved in our structure, indicating N protein is a promising drug target. In addition, certain areas of N-NTD and N-CTD display distinct charge distribution patterns in SARS-CoV-2, which may alter the RNA-binding modes. The specific antigenic characteristics are critical for developing specific immune-based rapid diagnostic tests. Our structural information can aid in the discovery and development of antiviral inhibitors against SARS-CoV-2 in the future.

We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2␣ is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2␣ is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by expansion of endogenous NC territories. AP2␣ also has the property of inducing NC in isolated ectoderm in which Wnt signaling is provided but BMP signaling is minimized by overexpression of chordin. Like other NC regulatory factors, activation of AP2␣ requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2␣. Furthermore, AP2␣ expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2␣ morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2␣ in NC induction. We propose a model in which AP2␣ expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2␣, Sox9, and Slug, leading to and maintaining NC specification.bone morphogenetic protein ͉ Wnt ͉ Sox9 ͉ Slug ͉ morpholino antisense oligonucleotides