The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous loss worldwide. Although viral spike (S) protein binding of angiotensin-converting enzyme 2 (ACE2) has been established, the functional consequences of the initial receptor binding and the stepwise fusion process are not clear. By utilizing a cell–cell fusion system, in complement with a pseudoviral infection model, we found that the spike engagement of ACE2 primed the generation of S2′ fragments in target cells, a key proteolytic event coupled with spike-mediated membrane fusion. Mutagenesis of an S2′ cleavage site at the arginine (R) 815, but not an S2 cleavage site at arginine 685, was sufficient to prevent subsequent syncytia formation and infection in a variety of cell lines and primary cells isolated from human ACE2 knock-in mice. The requirement for S2′ cleavage at the R815 site was also broadly shared by other SARS-CoV-2 spike variants, such as the Alpha, Beta, and Delta variants of concern. Thus, our study highlights an essential role for host receptor engagement and the key residue of spike for proteolytic activation, and uncovers a targetable mechanism for host cell infection by SARS-CoV-2.
Graphical AbstractHighlights d The surface tension of mESC colony is dynamically evolved during proliferation d A 3D supracellular actomyosin cortex assembles around the colony surface of mESCs d The compressive stress inside mESC colony facilitates pluripotency gene expression d The 3D supracellular actomyosin cortex contributes to blastocyst development
In BriefCells in an embryonic stem cell colony synergistically generate compression force by dynamically assembled cytoskeleton to facilitate the maintenance of colony morphology and pluripotency gene expression.
Seroprevalence of Toxoplasma gondii infection in fattening pigs in Heilongjiang Province, northeast China, was investigated between July 2011 and June 2012. In total, 1,014 pig serum samples were collected from 10 administrative regions and assayed for T. gondii antibodies by indirect hemagglutination (IHA) test using a commercially available kit. The average T. gondii antibody-positive prevalence was 4.6% (47/1,014), which is relatively lower than that in other provinces in China. Seroprevalence in fattening pigs raised on small farms (6.3%) was significantly higher than that on large farms (3.8%) (P < 0.05), and the seroprevalence ranged from 2.4% (Shuangyashan) to 6.8% (Qitaihe) between different geographical regions. Given that pork is not examined for T. gondii infection in China by law, these findings have public health implications and provide useful baseline information for the control of pig toxoplasmosis in this unique region of China.
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