The Role of Human Mobility Flow in the Region-to-Region Spread of Respiratory Syncytial Virus Infection among Infants: An Infographic Analysis.

The region-to-region spread of human infectious diseases is considered to be dependent on the human mobility flow (HMF). However, it has been hard to obtain the evidence for this. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic in Japan 2020, the government has enforced countermeasures against COVID-19 nationwide, namely the restriction of personal travelling, universal masking, and hand hygiene. As a result, the spread of acute respiratory infections had been effectively controlled. However, COVID-19 as well as pediatric respiratory syncytial virus (RSV) infections were not well-controlled. The region-to-region spread of pediatric RSV infections in 2020-2021 was recognizable unlike those in 2018 and 2019. In this study, we investigated the correlation between the trend of regional reports of the pediatric RSV infections and the HMF based on cellular phone signal data. Upon closer examination of both epidemiological trend and HMF data, the spread of pediatric RSV infection from one region to another was logically explained by HMF, which would serve as the evidence of the dependence of regional transmission on HMF. This is the first solid evidence where this correlation has been clearly observed for the common respiratory infections. While social implementation of infection control measures has successfully suppressed the droplet-mediated respiratory infections, such as influenza, but not the airborne infections, it was suggested that the aerosol transmission and adult asymptomatic carrier were involved in the transmission of RSV akin to COVID-19.

Sphingomyelin synthase 1 supports two steps of rubella virus life cycle.

Our knowledge of the regulatory mechanisms that govern the replication of the rubella virus (RV) in human cells is limited. To gain insight into the host-pathogen interaction, we conducted a loss-of-function screening using the CRISPR-Cas9 system in the human placenta-derived JAR cells. We identified sphingomyelin synthase 1 (SGMS1 or SMS1) as a susceptibility factor for RV infection. Genetic knockout of SGMS1 rendered JAR cells resistant to infection by RV. The re-introduction of SGMS1 restored cellular susceptibility to RV infection. The restricted step of RV infection was post-endocytosis processes associated with the endosomal acidification. In the late phase of the RV replication cycle, the maintenance of viral persistence was disrupted, partly due to the attenuated viral gene expression. Our results shed light on the unique regulation of RV replication by a host factor during the early and late phases of viral life cycle.

Isolation of induced pluripotent stem cell-derived endothelial progenitor cells from sac-like structures.

Transplanted endothelial progenitor cells (EPCs) repair blood vessels and exert regenerative effects on disorders such as lower limb ischemia. EPCs serve as a model for pathophysiological and pharmacokinetic studies, which is important for drug discovery. However, primary human EPCs are phenotypically unstable, which limits their clinical utility. Therefore, we employed human induced pluripotent stem (iPS) cells to circumvent this problem. Here we focused on human iPS cell-derived sac-like structures (iPS-sacs), which contain endothelial lineage cells and hematopoietic lineage cells. Previous studies isolated only hematopoietic lineage cells from iPS-sacs. Therefore, here we attempted to isolate EPCs. However, iPS-sacs generated by a published protocol did not contain sufficient EPCs. Therefore, to generate iPS-sacs highly enriched in EPCs, we added the glycogen synthase kinase 3 beta (GSK3ß) inhibitor CHIR-99021 to the culture medium early during differentiation. The cells rapidly differentiated into mesoderm to yield abundant EPCs, and CHIR-99021 increased the proportion of EPCs contained in iPS-sacs. EPCs, which were purified using anti-platelet endothelial cell adhesion molecule (PECAM1) antibody-conjugated beads, expressed markers of immature endothelial cells. Purified EPCs formed tube-like structures and incorporated acetylated low density lipoprotein (Ac-LDL), reflecting endothelial phenotypes. The simple method described here will likely improve regenerative medicine and facilitate basic studies on the endothelial lineage.