Biology subjects

Fukushi, H.

Publications and source records attributed to Fukushi, H..

4 recordsLinked to original sources

bioRxiv2025

Equine herpesvirus myeloencephalopathy-related mutations in EHV-1 DNA polymerase allow EHV-1 to grow at elevated temperatures

Equine herpesvirus myeloencephalopathy (EHM) caused by equine herpesvirus type 1 (EHV-1) is a major threat to the equine industry because of its devastatating impact on animal welfare and performance. A specific single nucleotide polymorphism (SNP) (G2254/D752) in the EHV-1 ORF30 gene encoding DNA polymerase was previously shown to be a marker of the strain of EHV-1 that causes EHM. However, the effect of this SNP has never been resolved. Clinical findings indicated that fever and higher viremia levels are associated with the onset of EHM. No studies have examined EHV-1 growth at elevated temperatures so far. We found that EHV-1 with the D752 SNP replicated at elevated temperatures, and EHV-1 without it did not. We also found that EHV-1s isolated from horses with EHM could grow at elevated temperatures and most non-EHM isolates were suppressed by elevated temperatures. EHV-1s that can replicate at elevated temperatures have this SNP or one other SNP in ORF30. This appears to be the first report to show an association between EHM and the ability of EHV-1 to grow at elevated temperatures. (177 words) ImportanceEquine herpesvirus myeloencephalopathy (EHM) caused by equine herpesvirus type 1 (EHV-1) is a major threat to the equine industry because of its impact on animal welfare and performance. A specific single nucleotide polymorphism (SNP) (G2254/D752) in EHV-1 ORF30 gene encoding DNA polymerase (UL30) was previously shown to be a marker of EHM. However, the effect of this SNP has never been resolved. Here we show that this and one other SNP in UL30 are associated with replication capacity at elevated temperatures. (81 words)

microbiology↗

bioRxiv2022

Unique genomic sequences in novel Mycobacterium avium subsp. hominissuis lineage enabled fine scale tracing the transmission route during pig movement

Mycobacterium avium subsp. hominissuis (MAH) is one of the most prevalent mycobacteria causing non-tuberculous mycobacterial disease in humans and animals. Of note, MAH is a major cause of mycobacterial granulomatous mesenteric lymphadenitis outbreaks in pig populations. To determine the precise source of infection of MAH in a pig farm and to clarify the epidemiological relationship among pig, human and environmental MAH lineages, we collected 50 MAH isolates from pigs reared in Japan and determined draft genome sequences of 30 isolates. A variable number of tandem repeat analysis revealed that most pig MAH isolates in Japan were closely related to North American, European and Russian human isolates but not to those from East Asian human and their residential environments. Historical recombination analysis revealed that most pig isolates could be classified into SC2/4 and SC3, which contain MAH isolated from pig, European human and environmental isolates. Half of the isolates in SC2/4 had many recombination events with MAH lineages isolated from humans in East Asia. To our surprise, four isolates belonged to a new lineage (SC5) in the global MAH population. Members of SC5 had few footprints of inter-lineage recombination in the genome, and carried 80 unique genes, most of which were located on lineage specific-genomic islands. Using unique genetic features, we were able to trace the putative transmission route via their host pigs. Together, we clarify the possibility of species-specificity of MAH in addition to local adaptation. Our results highlight two transmission routes of MAH, one exposure on pig farms from the environment and the other via pig movement. Moreover, our study also warns that the evolution of MAH in pigs is influenced by MAH from patients and their residential environments, even if the MAH are genetically distinct. HighlightsO_LIVariable number of tandem repeat analysis of Mycobacterium avium subsp. hominissuis (MAH) isolated from pigs (n=50) were conducted. C_LIO_LIDraft genome sequences of MAH (n=30) and genome analysis were conducted. C_LIO_LIPig MAHs were genetically far from East Asian human isolates and close to those of Western countries. C_LIO_LINovel MAH lineage which were transmitted farms by pig movement was found. C_LIO_LIHuman MAH isolates influenced the evolution of pig isolates. C_LI

microbiology↗

bioRxiv2021

Genomic features of Mycobacterium avium subsp. hominissuis isolated from pigs in Japan.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most important agents causing non-tuberculosis mycobacterial infection in humans and pigs. Genome analysis on MAH of human isolates has been proceeding, however, those of pigs are limited despite its potential source of infection to human. In the current study, we obtained 30 draft genome sequences of MAH of pigs reared in Japan. The 30 draft genomes consisted of 4,848,678 - 5,620,788 bp length, 4,652 - 5,388 coding genes and 46 - 75 (Med: 47) tRNAs. All isolates had restriction modification associated genes and 185 - 222 predicted virulence genes. Two isolates had tRNA arrays and one isolate had a clustered regularly interspaced short palindromic repeat (CRISPR) region. Our results will be useful for evaluation of the ecology of MAH by providing a foundation for genome-based epidemiological studies.

microbiology↗

bioRxiv2018

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response

Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective and cell active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells, is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 resulted in drastically reduced levels of arginine monomethylation of HSP70 family members and other stress-associated proteins. Structural and biochemical analysis revealed that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibited methylation of both constitutive and inducible forms of HSP70, and led to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.

biochemistry↗