Biology subjects

Moriyama, H.

Publications and source records attributed to Moriyama, H..

9 recordsLinked to original sources

bioRxiv2026

A single-stranded DNA virus replicates in the mitochondria of a marine oomycete

A virus with a circular single-stranded DNA genome, HthCRESSV1, was discovered in an oomycete, Halophytophthora thermoambigua, isolated from brackish waters off the Algarve coast in southern Portugal. Phylogenetic analyses place this virus outside of all currently classified families within the phylum Cressdnaviricota, suggesting it represents a distinct lineage. Cellular fractionation, mitochondrial marker co-enrichment, and Southern blot analyses indicate that HthCRESSV1 is associated with mitochondria and replicates episomally. The virus is stably transmitted through zoospores and, notably, infected host isolates are associated with reduced growth and changes in temperature-dependent performance. Homologous sequences corresponding to both the replication-associated protein and a membrane-associated hypothetical protein were identified in the mitochondrial genomes of several oomycete species, suggesting recurrent endogenization of HthCRESSV1-like viruses in oomycete mitochondria. Together, these findings expand the known diversity of oomycete-associated DNA viruses, identify mitochondria as an unexpected niche for DNA virus replication, and highlight marine environments as underexplored reservoirs of DNA viruses in stramenopiles.

evolutionary biology↗

bioRxiv2026

In vivo xenogenic reconstitution of human alveolar epithelial architecture and function

An urgent need exists for lung models that accurately replicate human physiological profiles. We developed a chimeric mouse model enabling targeted ablation of alveolar type 2 (AT2) cells and lung macrophages, creating niches for endoscopically transplanted human induced pluripotent stem cell (hiPSC)-derived lung progenitors (hLPs). These engrafted cells were retained for 24 weeks, demonstrating self-renewal and differentiation potential, surfactant protein secretion, and maintaining alveolar phosphate homeostasis, suggesting their maturation into AT2 cells. Furthermore, transplantation of hLPs derived from disease-specific hiPSCs recapitulated the phenotype of pulmonary alveolar microlithiasis. The architecture, function, and metabolism of human alveolar epithelium were accurately replicated in vivo. This model has the potential to link experimental models and first-in-human studies, facilitating the development of novel therapies for intractable lung diseases.

developmental biology↗

bioRxiv2024

Novel endornaviruses infecting Phytophthora cactorum that attenuate vegetative growth, promote sporangia formation, and confer hypervirulence to the host oomycete.

Two novel endornaviruses were found in Phytophthora cactorum isolated from severe black lesions on Boehmeria nivea (B. nivea) var. nipononivea plants in a Japanese forest. These two endornaviruses were named Phytophthora cactorum alphaendornavirus 4 (PcAEV4) and Phytophthora cactorum alphaendornavirus 5 (PcAEV5), and have site-specific nick structures in their positive RNA strands, which are hallmarks of alphaendornaviruses. Ribavirin and cycloheximide treatment of the protoplasts effectively cured the host oomycete (Kara1) of the viruses. The resultant virus-free strain (Kara1-C) displayed luxuriant mycelial growth with less zoosporangia formation as compared to the Kara1 strain. Remarkably, the Kara1-C strain exhibited reduced ability to form black lesions on B. nivea leaves, suggesting that presence of PcAEV4 and PcAEV5 in the Kara1 strain led to enhanced virulence in host plants. Under osmotic pressure and cell wall synthesis inhibition, the Kara1 strain exhibited less growth inhibition compared with the Kara1-C strain. In contrast, the Kara1 strain showed more growth inhibition to membrane-permeable surfactant compared with the Kara1-C strain, indicating that these endornaviruses can alter the susceptibility of the host oomycete to abiotic stresses. Co-localization and cell fractionation analyses showed that PcAEV4 and PcAEV5 localized to intracellular membranes, particularly the ER membrane fraction. Further, infection with these 2 endornaviruses was found to affect the hosts response to exogenous sterols, which enhanced vegetative growth and zoosporangia formation, as well as virulence of the host oomycete. These results provide deep insights into the effects of endornavirus infection in the Phytophthora spp. and also highlight protoplast-based methods in advancing Phytophthora virus studies.

microbiology↗

bioRxiv2024

Identification of a novel mycovirus belonging to the ''flexivirus''-related family with icosahedral virion

The order Tymovirales currently comprises five viral families with positive-sense RNA ((+)RNA) genomes that infect plants, fungi, and insects. Virion morphologies within the order Tymovirales differ between families, with icosahedral virions in the Tymoviridae and filamentous virions in the other "flexi"viridae families. Despite their different morphologies, these viruses are placed in the same order based on phylogenetic analyses of replicase-associated polyproteins. However, one of the families in the Tymovirales, Deltaflexiviridae, is considered to be capsidless because there have been no published reports of virion isolation. Here we report that a new "flexivirus"-related (+)RNA virus, prospectively named Fusarium oxysporum icosahedral virus 1 (FoIV1), is icosahedral, and that most deltaflexiviruses may have icosahedral virions. Phylogenetic analyses based on replicase-associated polyproteins indicated that FoIV1 forms a distinct group in the Tymovirales with some viruses originally assigned to the Deltaflexiviridae. Electron microscopy, protein analysis, and protein structure predictions indicate that FoIV1 ORF4 encodes a single jelly-roll (SJR)-like coat protein (CP) that constitutes the icosahedral virions. Results of clustering analyses based on amino acid sequences and predicted CP structures suggested that most of the deltaflexiviruses have icosahedral virions composed of SJR-like CPs as in FoIV1, rather than having filamentous virions or capsidless. These results challenge the conventional understanding of viruses in the order Tymovirales, with important implications for revising its taxonomic framework and providing insights into the evolutionary relationships within this diverse and broad host range group of (+)RNA viruses.

microbiology↗

bioRxiv2024

The Co-Evolution of Jawed Vertebrates and Interferon Regulatory Factor 5 Generates Unique Inflammation and Innate Immunity

The emergence of jaws in early vertebrates introduced a novel feeding apparatus and potent oral defenses but also increased the risk of physical injury and pathogen exposure. Innate immunity and inflammation constitute the bodys first line of defense against invading microbes and tissue damage, aiming to eliminate threats and restore internal homeostasis. Interferon regulatory factor 5 (IRF5) plays a critical role in orchestrating innate immunity and inflammation by regulating the transcription of genes that encode type I interferons (IFNs) and pro-inflammatory cytokines. Despite this, the evolution of IRF5 has remained poorly understood. We have identified the IRF5 and IRF6 genes in cartilaginous fish, including sharks. As cartilaginous fish represent one of the oldest surviving jawed vertebrate lineages, the presence of these genes suggests the genes have ancient origins potentially dating back hundreds of millions of years to early jawed vertebrates. Furthermore, our analysis shows that IRF5 has conserved nuclear export sequences and phosphorylation sites for activation throughout evolution from cartilaginous fish to humans, indicating these regulatory elements evolved early and have been maintained across jawed vertebrates. Additionally, the shift in subcellular localization of IRF5 from nucleus to cytosol, and of other interferon related IRFs, aligns with functional enhancements of IRFs in innate immunity and the emergence of IFNs across jawed vertebrates. This analysis implies that the evolution of jaws may have driven the emergence of new IRF members, the expansion of their functions, and the development of a unique inflammation and innate immune system.

immunology↗

bioRxiv2023

Nitrogen signaling factor triggers a respiration-like gene expression program

Microbes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response to changes in their immediate environment. In the fission yeast Schizosaccharomyces pombe, the oxylipin Nitrogen Signaling Factor (NSF) is part of such communication system, which functions to regulate the usage of different nitrogen sources. Yet, the pathways and mechanisms by which NSF acts are poorly understood. Here, we show that NSF physically interacts with the mitochondrial sulfide:quinone oxidoreductase Hmt2 and that it prompts a change from a fermentation- to a respiration-like gene expression program independently of the carbon source. Our results suggest that NSF activity is not restricted to nitrogen metabolism alone and that it could function as a rheostat to prepare a population of S. pombe cells for an imminent shortage of their preferred nutrients.

microbiology↗

bioRxiv2023

Bidirectional feedforward regulatory loop of Dicer-like 4 and flavonoids causes floral bicolor patterning in petunia and dahlia

Floral bicolor pigmentation is caused by naturally occurring RNA interference (RNAi) in some cultivars of petunia and dahlia. In both plants, the chalcone synthase gene is highly expressed only in the pigmented region of bicolor petals. However, it remains unknown why RNAi is induced only in the unpigmented region. To elucidate the mechanism of this clear bicolor pattern formation, we examined the dicing activity of Dicer-like 4 (DCL4), which produces small interfering RNAs essential for the induction of RNAi. We showed that the crude extract in the pigmented petal region inhibits dicing activity of DCL4, but not when flavonoids were depleted from the extract. Moreover, we showed the inhibitory activity was associated with flavonoid aglycons. The in vivo dicing activities were detected in the intact protoplasts prepared from the unpigmented region but not from the pigmented region. These results suggest that in the unpigmented region, flavonoids that inhibit DCL4 are not synthesized, and RNAi is maintained, whereas in the pigmented region, DCL4 is inhibited by flavonoids, RNAi is not induced, and anthocyanin biosynthesis is maintained, which ensures RNAi inhibition. Therefore, a clear bicolor pattern is generated by the bidirectional feedforward mechanism of antagonizing DCL4 and flavonoids.

plant biology↗

bioRxiv2021

Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle metabolon which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was presented together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.

biochemistry↗

bioRxiv2020

Evolved increases in hemoglobin-oxygen affinity and Bohr effect coincided with the aquatic specialization of penguins.

Dive capacities of air-breathing vertebrates are dictated by onboard O2 stores, suggesting that physiological specializations of diving birds like penguins may have involved adaptive changes in convective O2 transport. It has been hypothesized that increased hemoglobin (Hb)-O2 affinity improves pulmonary O2 extraction and enhance capacities for breath-hold diving. To investigate evolved changes in Hb function associated with the aquatic specialization of penguins, we integrated comparative measurements of whole-blood and purified native Hbs with protein engineering experiments based on site-directed mutagenesis. We reconstructed and resurrected ancestral Hbs representing the common ancestor of penguins and the more ancient ancestor shared by penguins and their closest nondiving relatives (order Procellariiformes, which includes albatrosses, shearwaters, petrels, and storm petrels). These two ancestors bracket the phylogenetic interval in which penguin-specific changes in Hb function would have evolved. The experiments revealed that penguins evolved a derived increase in Hb-O2 affinity and a greatly augmented Bohr effect (reduced Hb-O2 affinity at low pH). Although an increased Hb-O2 affinity reduces the gradient for O2 diffusion from systemic capillaries to metabolizing cells, this can be compensated by a concomitant enhancement of the Bohr effect, thereby promoting O2 unloading in acidified tissues. We suggest that the evolved increase in Hb-O2 affinity in combination with the augmented Bohr effect maximizes both O2 extraction from the lungs and O2 unloading from the blood, allowing penguins to fully utilize their onboard O2 stores and maximize underwater foraging time.

evolutionary biology↗