Biology subjects

Ohkawa, A.

Publications and source records attributed to Ohkawa, A..

3 recordsLinked to original sources

bioRxiv2026

Development of a Synthetic Genomics-Based Venezuelan Equine Encephalitis Virus Expressing Secreted Gaussia Luciferase for High-Throughput Antiviral Screening

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that causes severe neurological disease in humans and animals. Despite its public health importance, no approved antiviral therapy is currently available, and conventional methods for quantifying infectious virus are labor-intensive and poorly suited for high-throughput antiviral screening. Furthermore, research on VEEV is complicated by the restricted availability and international transport of infectious viral materials. Here, we established a full-length infectious cDNA clone of VEEV entirely from chemically synthesized DNA fragments and rescued recombinant reporter viruses expressing mCherry2, ZsGreen, or the secreted Gaussia luciferase mutant 23 (GLucM23). The reporter viruses retained replication kinetics comparable to those of wild-type VEEV, while the fluorescent reporters enabled direct visualization of infection and virus-induced cytopathic effects. GLucM23-expressing VEEV allowed rapid, sensitive, and non-destructive quantification of viral replication directly from culture supernatants, enabling repeated longitudinal measurements without disrupting infected cells. We further demonstrated the utility of this system by screening approximately 3,000 FDA-approved compounds to identify inhibitors of VEEV replication. Together, these findings establish a versatile synthetic genomics-based reporter virus platform for quantitative studies of VEEV replication and scalable antiviral drug discovery.

microbiology↗

bioRxiv2023

Conserved use of the sodium/bile acid cotransporter (NTCP) as an entry receptor by hepatitis B virus and domestic cat hepadnavirus

The Orthohepadnavirus genus includes hepatitis B virus (HBV) that can cause chronic hepatitis and hepatocarcinoma in humans. Recently, a novel hepadnavirus in cats, domestic cat hepadnavirus (DCH), was identified that is genetically close to HBV. DCH infection is associated with chronic hepatitis in cats, suggesting a similarity with HBV pathogenesis and the potential to use DCH as a novel animal model for HBV research. HBV is shown to use the sodium/bile acid cotransporter (NTCP) as a major cell entry receptor, but the equivalent receptor for DCH remains unknown. Here we sought to identify the entry receptor for DCH. HBV- and DCH-derived preS1 peptides efficiently bound to both human and cat NTCPs, and residue 158 of NTCP proteins determined the species-specific binding of the DCH preS1 peptide. Myrcludex B, an HBV entry inhibitor, blocked binding of the DCH preS1 peptide. Thus, DCH and HBV may share cell entry molecules, suggesting a possibility of inter-species transmission. Furthermore, our study suggests that DHC can be useful as a novel model for HBV research.

microbiology↗

bioRxiv2020

fMRI-guided white matter connectivity in fluid and crystallized cognitive abilities in healthy adults

This study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction, the mean percent signal change for the episodic memory showed positive associations with behavioral performance, and the associations between MD and percent signal change differed by age such that, when divided into three age groups to further explore this interaction, only the oldest age group show a significant negative correlation between the two brain measures. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the abilitys greater resistance against aging.

neuroscience↗