Biology subjects

Makino, A.

Publications and source records attributed to Makino, A..

5 recordsLinked to original sources

bioRxiv2023

Genome-scale CRISPR-Cas9 screen identifies novel host factors as potential therapeutic targets for SARS-CoV-2 infection.

Although many host factors important for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, the mechanisms by which the virus interacts with host cells remain elusive. Here, we identified tripartite motif containing (TRIM) 28, TRIM33, euchromatic histone lysine methyltransferase (EHMT) 1, and EHMT2 as novel proviral factors involved in SARS-CoV-2 infection by CRISPR-Cas9 screening. We demonstrated that TRIM28 plays a role(s) in viral particle formation and that TRIM33, EHMT1, and EHMT2 are involved in viral transcription and replication using cells with suppressed gene expression. UNC0642, a compound that specifically inhibits the methyltransferase activity of EHMT1/2, strikingly suppressed SARS-CoV-2 growth in cultured cells and reduced disease severity in a hamster infection model. This study suggests that EHMT1/2 may be a novel therapeutic target for SARS-CoV-2 infection.

microbiology↗

bioRxiv2022

Contact-number-driven virus evolution: a multi-level modeling framework for the evolution of acute or persistent RNA virus infection

Viruses evolve in infected host populations, and host population dynamics affect viral evolution. RNA viruses with a short duration of infection and a high peak viral load, such as and SARS-CoV-2, are maintained in human populations. By contrast, RNA viruses characterized by a long infection duration and a low peak viral load (e.g., borna disease virus) can be maintained in nonhuman populations, and why the persistent viruses evolved has been rarely explored. Here, using a multi-level modeling approach including both individual-level virus infection dynamics and population-scale transmission, we consider virus evolution based on the host environment, specifically, the effect of the contact history of infected hosts. We found that, with a highly dense contact history, viruses with a high virus production rate but low accuracy are likely to be optimal, resulting in a short infectious period with a high peak viral load. In contrast, with a low-density contact history, viral evolution is toward low virus production but high accuracy, resulting in long infection durations with low peak viral load. Our study sheds light on the origin of persistent viruses and why acute viral infections but not persistent virus infection tends to prevail in human society.

evolutionary biology↗

bioRxiv2022

Ban on wild bird importation accelerated the spread of global viral outbreaks in parrots.

Since the isolation of the first parrot bornavirus (PaBV), which causes slow-onset, fatal neurological disease in various parrot species, in the United States in 2008, PaBVs have spread rapidly worldwide; however, the reason remains unknown. In this study, we show that the most dominant lethal genotype, PaBV-4, spread via the global trade of captive birds. Analyses of traded parrot numbers in the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) database and PaBV-4 phylodynamics suggested that the ban of wild imported birds in the European Union (EU) in 2007 facilitated the international trade of captive parrots, which resulted in an increase in the effective population size of PaBV-4. This change coincided with a historical PaBV-4 epidemic. These data suggest that due to the low transmission efficiency and long incubation period of PaBV-4, the majority of PaBV-4 transmission occurred in breeding facilities and the increased trade of captive parrots accelerated the global spread of PaBV-4 infection. Our results indicate that interventions for the protection of wild animals and prevention of infectious diseases may conversely cause epidemics of infectious diseases in the global system. Conservation of ecosystems requires not only the establishment of importation restrictions and maintenance of the diversity of wild animals but also the implementation of multifaceted management measures, such as quarantine policies and breeding control in captive animals.

microbiology↗

bioRxiv2021

Membrane cholesterol interferes with tyrosine phosphorylation but facilitates the clustering and signal transduction of EGFR

Epidermal growth factor receptor (EGFR) activates major cell signaling pathways that regulate various cell responses. Its dimerization and clustering coupled with its lateral mobility are critical for EGFR function, but the contribution of the plasma membrane environment to EGFR function is unknown. Here we show, using single-molecule analysis, that EGFR mobility and clustering are altered by the depletion of cholesterol or sphingomyelin, major lipids of membrane subdomains, causing significant changes in EGFR signaling. When cholesterol was depleted, the subdomain boundary in EGFR diffusion disappeared, the fraction of EGFR pre-dimers was increased, and the ligand-induced phosphorylation of EGFR was enhanced. In addition, the depletion of either lipid prevented the formation of immobile clusters after EGF association and decreased the phosphorylation of downstream proteins. Our results revealed that cholesterol plays dichotomous roles in the signaling pathway of EGFR and that clustering in the membrane subdomains is critical for EGFR signal transduction.

biophysics↗

bioRxiv2021

Manganese toxicity disrupts indole acetic acid homeostasis and suppresses CO2 assimilation reaction in rice plants

Despite the essentiality of Mn in terrestrial plants, its excessive accumulation in plant tissues causes growth defects, known as Mn toxicity. Mn toxicity can be divided into apoplastic and symplastic types depending on its onset. For growth defects, symplastic rather than apoplastic Mn toxicity is hypothesised to be more critical. However, details of the relationship between growth defects and symplastic Mn toxicity remains elusive. In this study, we aimed to elucidate the molecular mechanisms of symplastic Mn toxicity in rice plants. We found that under excess Mn conditions, CO2 assimilation was inhibited by stomatal closure, and both carbon anabolic and catabolic activities were decreased. In addition to stomatal dysfunction, stomatal and leaf anatomical development were also altered by excess Mn accumulation. Furthermore, the indole acetic acid (IAA) concentration was decreased, and auxin-responsive gene expression analyses showed IAA-deficient symptoms in leaves due to excess Mn accumulation. These results suggest that excessive Mn accumulation causes IAA deficiency, and low IAA concentrations suppress plant growth by suppressing stomatal opening and leaf anatomical development for efficient CO2 assimilation in leaves. HIGHLIGHTIncreased Mn concentration lowers auxin concentrations in rice leaves, which suppresses photosynthesis by changing stomatal function and development.

plant biology↗