Biology subjects

Komorizono, R.

Publications and source records attributed to Komorizono, R..

4 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↗

bioRxiv2023

Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution

During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution.

evolutionary biology↗

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↗