Heterologous vaccination utilizing viral vector and protein platforms confers complete protection against SFTSV.

Severe fever with thrombocytopenia syndrome virus was first discovered in 2009 as the causative agent of severe fever with thrombocytopenia syndrome. Despite its potential threat to public health, no prophylactic vaccine is yet available. This study developed a heterologous prime-boost strategy comprising priming with recombinant replication-deficient human adenovirus type 5 (rAd5) expressing the surface glycoprotein, Gn, and boosting with Gn protein. This vaccination regimen induced balanced Th1/Th2 immune responses and resulted in potent humoral and T cell-mediated responses in mice. It elicited high neutralizing antibody titers in both mice and non-human primates. Transcriptome analysis revealed that rAd5 and Gn proteins induced adaptive and innate immune pathways, respectively. This study provides immunological and mechanistic insight into this heterologous regimen and paves the way for future strategies against emerging infectious diseases.

J2N-k hamster model simulates severe infection caused by severe acute respiratory syndrome coronavirus 2 in patients with cardiovascular diseases.

Considering the global impact of the coronavirus disease 2019 (COVID-19) pandemic, generating suitable experimental models is imperative. For pre-clinical studies, researchers require animal models displaying pathological features similar to those observed in patients; therefore, establishing animal models for COVID-19 is crucial. The golden Syrian hamster model mimics conditions observed in humans with mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a golden Syrian hamster model of severe infection has not been reported. J2N-k hamsters are utilized as a cardiomyopathy model; therefore, we used cardiomyopathic J2N-k hamsters showing conditions similar to those of severe COVID-19 complicated with cardiovascular diseases, as patients with cardiovascular diseases exhibit a higher risk of morbidity and mortality due to COVID-19 than patients without cardiovascular diseases. Unlike that in golden Syrian hamsters, SARS-CoV-2 infection was lethal in J2N-k hamsters, with a median lethal dose of 104.75 plaque-forming units for the S clade of SARS-CoV-2 (A, GenBank: MW466791.1). High viral titers and viral genomes were detected in the lungs of J2N-k and golden Syrian hamster models harvested 3 days after infection. Pathological features of SARS-CoV-2-associated lung injury were observed in both models. The J2N-k hamster model can aid in developing vaccines or therapeutics against COVID-19.

Comparison of SARS-CoV-2 variant lethality in human angiotensin-converting enzyme 2 transgenic mice.

This study compared the lethality of severe acute respiratory syndrome coronavirus 2 variants belonging to the S, V, L, G, GH, and GR clades using K18-human angiotensin-converting enzyme 2 heterozygous mice. To estimate the 50% lethal dose (LD50) of each variant, increasing viral loads (100-104 plaque-forming units [PFU]) were administered intranasally. Mouse weight and survival were monitored for 14 days. The LD50 of the GH and GR clades was significantly lower than that of other clades at 50 PFU. These findings suggest that the GH and GR clades, which are prevalent worldwide, are more virulent than the other clades.

WasC, a WASP family protein, is involved in cell adhesion and migration through regulation of F-actin polymerization in Dictyostelium.

The actin cytoskeleton is involved in the regulation of cell morphology and migration. Wiskott-Aldrich Syndrome proteins (WASPs) play an important role in controlling actin polymerization by activating the Arp2/3 complex. The present study investigated the roles of WasC, one of the 3 WASPs in Dictyostelium, in cellular processes. Cells lacking WasC displayed strong cell adhesion and approximately 1.5-fold increase in F-actin levels as compared to the wild-type cells. Loss of wasC caused defects in phagocytosis and decreased the migration speed in chemoattractant-mediated cell migration but did not affect directionality. WasC was localized to the protruding region in migrating cells and, transiently and rapidly translocated to the cell cortex in response to chemoattractant stimulation, in an F-actin dependent manner. Our results suggest that WasC is involved in cell adhesion and migration by regulating F-actin polymerization at the leading edge of migrating cells, probably as a negative regulator. The increased strength of adhesion in wasC null cells is likely to decrease the migration speed but not the directionality.

Cell migration directionality and speed are independently regulated by RasG and Gß in Dictyostelium cells in electrotaxis.

Motile cells manifest increased migration speed and directionality in gradients of stimuli, including chemoattractants, electrical potential and substratum stiffness. Here, we demonstrate that Dictyostelium cells move directionally in response to an electric field (EF) with specific acceleration/deceleration kinetics of directionality and migration speed. Detailed analyses of the migration kinetics suggest that migration speed and directionality are separately regulated by Gß and RasG, respectively, in EF-directed cell migration. Cells lacking Gß, which is essential for all chemotactic responses in Dictyostelium, showed EF-directed cell migration with the same increase in directionality in an EF as wild-type cells. However, these cells failed to show induction of the migration speed upon EF stimulation as much as wild-type cells. Loss of RasG, a key regulator of chemoattractant-directed cell migration, resulted in almost complete loss of directionality, but similar acceleration/deceleration kinetics of migration speed as wild-type cells. These results indicate that Gß and RasG are required for the induction of migration speed and directionality, respectively, in response to an EF, suggesting separation of migration speed and directionality even with intact feedback loops between mechanical and signaling networks.