SARS-CoV-2, a β-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.

BackgroundNon-severe acute respiratory syndrome (non-SARS)-related human coronaviruses (HCoVs), including HCoV-229E, -HKU1, -NL63, and -OC43, have been detected in respiratory tract samples from children and adults. However, the natural prevalence of antibodies against these viruses in serum among population is unknown.MethodsTo measure antibodies to the spike (S) protein of the four common non-SARS HCoVs, recombinant S proteins of the four HCoVs were expressed and characterised in 293 T cell. An S-protein-based indirect immunofluorescence assay (IFA) was then developed to detect anti-S IgG and IgM for the four individual HCoVs and applied to serum samples from a general asymptomatic population (218 children and 576 adults) in Beijing.ResultsOf 794 blood samples tested, only 29 (3.65%) were negative for anti-S IgG. The seropositivity of the four anti-S IgG antibodies was >70% within the general population. The majority of seroconversions to four-HCoV positivity first occurred in children. Both S-IgG and S-IgM antibodies were detectable among children and increased with age, reaching a plateau at 6 years of age. However, no anti-S IgM was detected in healthy adults.ConclusionLarge proportions of children and adults in Beijing have evidence of anti-S IgG against four the HCoVs, and first infections by all four non-SARS HCoVs takes place during childhood.

In Alzheimer's disease (AD), structural and functional brain network organization is disturbed. However, many of the present network analysis measures require a priori assumptions and methodological choices that influence outcomes and interpretations. Graph spectral analysis (GSA) is a more direct algebraic method that describes network properties, which might lead to more reliable results. In this study, GSA was applied to magnetoencephalography (MEG) data to explore functional network integrity in AD. Sensor-level resting-state MEG was performed in 18 Alzheimer patients (age 67 -9, 6 women) and 18 healthy controls (age 66 -9, 11 women). Weighted, undirected graphs were constructed based on functional connectivity analysis using the Synchronization likelihood, and GSA was performed with a focus on network connectivity, synchronizability, and node centrality. The main outcomes were a global loss of network connectivity and altered synchronizability in most frequency bands. Eigenvector centrality mapping confirmed the hub status of the parietal areas, and demonstrated a low centrality of the left temporal region in the theta band in AD patients that was strongly related to the mini mental state examination (global cognitive function test) score (r = 0.67, p = 0.001). Summarizing, GSA is a theoretically solid approach that is able to detect the disruption of functional network topology in AD. In addition to the previously reported overall connectivity losses and parietal area hub status, impaired network synchronizability and a clinically relevant left temporal centrality loss were found in AD patients. Our findings imply that GSA is valuable for the purpose of studying altered brain network topology and dynamics in AD.

Background/Aims: Interleukin-29 (IL-29), a critical member of type III interferons (IFNs) family, has been implicated in protecting against viral infection and modulating autoimmune inflammation. Toll-like receptor 4 (TLR4) plays a crucial role in synovial inflammation and may contribute to the pathogenesis of rheumatology arthritis (RA). However, little is known about the modifying effect of IL-29 on TLR4-mediated inflammation in RA. We aim to investigate the potential association between IL-29 and TLR4 in RA. Methods: Peripheral blood mononuclear cells (PBMCs) and serum from 77 patients with RA and 70 controls were collected to determine levels of IL-29 and TLR4 mRNA by real-time polymerase chain reaction (PCR). Levels of IL-29 and TLR4 in synovial tissues and fluid from 25 RA patients and 24 controls were detected by enzyme-linked immunosorbent assay (ELISA) or western blot assay, respectively. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-29. The production of inflammatory cytokines including IL-6, IL-8 as well as TNF-a and the activation of nuclear factor-κB (NF-κB) signaling were determined. Results: In comparison with controls, increased IL-29 was observed in PBMCs, synovial tissue, serum and synovial fluid of patients with RA. Besides, TLR4 was significantly elevated in PBMCs and synovium of RA patients. Moreover, IL-29 was positively associated with TLR4 in RA, suggested by Pearson's correlation analysis. When RAW264.7 cells were stimulated by LPS with or without IL-29 in vitro, IL-29 could enhance LPS-mediated TLR4 expression and the production of IL-6, IL-8 and TNF-a in RAW264.7 cells via the activation of NF-κB signaling. Conclusion: The present study suggests, for the first time, that IL-29 can aggravate LPS/TLR4-mediated inflammation in RA depending on NF-κB signaling activation.