资源环境科技发展态势分析平台

Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKC zeta and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.

Pneumonia resulting from infection is one of the leading causes of death worldwide. Pulmonary infection by the respiratory syncytial virus (RSV) is a large burden on human health, for which there are few therapeutic options(1). RSV targets ciliated epithelial cells in the airways, but how viruses such as RSV interact with receptors on these cells is not understood. Nucleolin is an entry coreceptor for RSV2 and also mediates the cellular entry of influenza, the parainfluenza virus, some enteroviruses and the bacterium that causes tularaemia(3,4). Here we show a mechanism of RSV entry into cells in which outside-in signalling, involving binding of the prefusion RSV-F glycoprotein with the insulin-like growth factor-1 receptor, triggers the activation of protein kinase C zeta (PKC zeta). This cellular signalling cascade recruits nucleolin from the nuclei of cells to the plasma membrane, where it also binds to RSV-F on virions. We find that inhibiting PKC zeta activation prevents the trafficking of nucleolin to RSV particles on airway organoid cultures, and reduces viral replication and pathology in RSV-infected mice. These findings reveal a mechanism of virus entry in which receptor engagement and signal transduction bring the coreceptor to viral particles at the cell surface, and could form the basis of new therapeutics to treat RSV infection.

Education is a key dimension of well-being and a crucial indicator of development(1-4). The Sustainable Development Goals (SDGs) prioritize progress in education, with a new focus on inequality(5-7). Here we model the within-country distribution of years of schooling, and use this model to explore educational inequality since 1970 and to forecast progress towards the education-related 2030 SDG targets. We show that although the world is largely on track to achieve near-universal primary education by 2030, substantial challenges remain in the completion rates for secondary and tertiary education. Globally, the gender gap in schooling had nearly closed by 2018 but gender disparities remained acute in parts of sub-Saharan Africa, and North Africa and the Middle East. It is predicted that, by 2030, females will have achieved significantly higher educational attainment than males in 18 countries. Inequality in education reached a peak globally in 2017 and is projected to decrease steadily up to 2030. The distributions and inequality metrics presented here represent a framework that can be used to track the progress of each country towards the SDG targets and the level of inequality over time. Reducing educational inequality is one way to promote a fairer distribution of human capital and the development of more equitable human societies.