Biology subjects

Matsuno, K.

Publications and source records attributed to Matsuno, K..

23 records · Page 2Linked to original sources

bioRxiv2022

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75

SARS-CoV-2 Omicron BA.2.75 emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically different from BA.5, the currently predominant BA.2 descendant. Here, we showed that the effective reproduction number of BA.2.75 is greater than that of BA.5. While the sensitivity of BA.2.75 to vaccination- and BA.1/2 breakthrough infection-induced humoral immunity was comparable to that of BA.2, the immunogenicity of BA.2.75 was different from that of BA.2 and BA.5. Three clinically-available antiviral drugs were effective against BA.2.75. BA.2.75 spike exhibited a profound higher affinity to human ACE2 than BA.2 and BA.5 spikes. The fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were comparable to those of BA.5 but were greater than those of BA.2. Our multiscale investigations suggest that BA.2.75 acquired virological properties independently of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.

microbiology↗

bioRxiv2022

Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5

Unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants imposes us to continuous control measurement. Given the rapid spread, new Omicron subvariant named BA.5 is urgently required for characterization. Here we analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1 comprehensively. Although in vitro growth kinetics of BA.5 is comparable among the Omicron subvariants, BA.5 become much more fusogenic than BA.1 and BA.2. The airway-on-a-chip analysis showed that the ability of BA.5 to disrupt the respiratory epithelial and endothelial barriers is enhanced among Omicron subvariants. Furthermore, in our hamster model, in vivo replication of BA.5 is comparable with that of the other Omicrons and less than that of the ancestral B.1.1. Importantly, inflammatory response against BA.5 is strong compared with BA.1 and BA.2. Our data suggest that BA.5 is still low pathogenic compared to ancestral strain but evolved to induce enhanced inflammation when compared to prior Omicron subvariants.

microbiology↗

bioRxiv2022

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2. HighlightsO_LISpike L452R/Q/M mutations increase the effective reproduction number of BA.2 C_LIO_LIBA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infections C_LIO_LIBA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2 C_LIO_LIBA.4/5 is more pathogenic than BA.2 in hamsters C_LI

microbiology↗

bioRxiv2021

Live imaging of delamination in Drosophila shows that epithelial cell motility and invasiveness are independently regulated

Delaminating cells undergo complex, precisely regulated changes in cell-cell adhesion, motility, polarity, invasiveness, and other cellular properties. Delamination occurs during development and in pathogenic conditions such as cancer metastasis. We analyzed the requirements for epithelial delamination in Drosophila ovary border cells, which detach from the structured epithelial layer and begin to migrate collectively. We used live imaging to examine cellular dynamics, particularly epithelial cells acquisition of motility and invasiveness, in delamination-defective mutants during the time period in which delamination occurs in the wild-type ovary. We found that border cells in slow border cells (slbo), a delamination-defective mutant, lacked invasive cellular protrusions but acquired motility, while JAK/STAT-inhibited border cells lost both invasiveness and motility. Our results indicate that invasiveness and motility, which are cooperatively required for delamination, are regulated independently. Our reconstruction experiments also showed that motility is not a prerequisite for acquiring invasiveness. Summary statementLive imaging of epithelial delamination reveals that cell motility and invasiveness, both of which are required for delamination, are regulated independently and that motility is not a prerequisite for invasiveness.

developmental biology↗

bioRxiv2020

Statistical validation verifies that enantiomorphic states of cell chirality are determinant dictating the left- or right-handed direction of the hindgut rotation in Drosophila

In the left-right (LR) asymmetric development of invertebrates, chirality of cells (cell chirality) plays crucial roles. Left- or right-handed structure of cells consequently directs the morphogenesis with corresponding LR asymmetry. In Drosophila, it has been suggested that cell chirality drives the LR-asymmetric development of various organs including the embryonic hindgut. However, this hypothesis is supported only by apparent concordance between these two events and by computer simulations connecting them [1-5]. Therefore, here, we mathematically evaluated the causal relationship between the cell chirality of the hindgut epithelial cells and the LR-directional rotation of the hindgut, which was previously postulated. Our logistic model obtained from various genetic backgrounds significantly explained the correlation between the enantiomorphic states of cell chirality and the LR directionality of hindgut rotation. This model also significantly explained the correlation between cell chirality stochastically formed in advance in each living embryo and the LR-directionality of the following rotation, suggesting the irrelevance of modes how cell chirality is formed. This analysis also showed that the cell chirality is not only sufficient but also required for the rotation. Considering the chronological order of these events, our study validated that cell chirality causally defines the LR asymmetry of the hindgut rotation.

developmental biology↗