Biology subjects

Shimoda, H.

Publications and source records attributed to Shimoda, H..

8 recordsLinked to original sources

bioRxiv2026

Distinct virus-specific regulation of RNA synthesis across genome segments by thogotovirus polymerases: insights from Oz virus and Dhori virus

Thogotoviruses are a group of tick-borne, six-segmented, negative-sense single-stranded RNA viruses. These viruses encode an RNA-dependent RNA polymerase that recognizes promoter sequences located at the genomic termini to initiate RNA synthesis. The 5' and 3' ends of the genome bind to the polymerase and function as a promoter. Outside the catalytic center, they base-pair with each other to form a double-stranded RNA structure. This structure is referred to as the distal duplex and plays an important role in RNA synthesis. In this study, we investigated how the RNA sequence of the distal duplex influences polymerase activity using minigenome systems of two thogotoviruses, Oz virus (OZV) and Dhori virus (DHOV). Each virus exhibits distinct activities among its six segments. In OZV, one determinant of these differences is the base pair at positions 5'12 and 3'11 within the distal duplex, where promoter activity varies depending on whether the base pair is G:C or A:U. In contrast, the DHOV polymerase is not affected by this difference. These results indicate that, even within the genus Thogotovirus, viruses differ in whether they possess a mechanism that modulates promoter activity based on subtle sequence differences within the distal duplex. Furthermore, phylogenetic analysis and comparison of promoter sequences suggest that thogotoviruses can be divided into groups that do or do not regulate intersegment promoter activity via the base pair at positions 5'12 and 3'11. HighlightsO_LIMinigenome systems of Oz virus and Dhori virus reveal segment-specific differences in promoter activity C_LIO_LIThe distal duplex sequence modulates RNA synthesis in a virus-dependent manner C_LIO_LIThe base pair at positions 5'12/3'11 determines promoter activity in Oz virus but not in Dhori virus C_LIO_LIThogotoviruses can be divided into groups that do or do not regulate promoter activity via distal duplex sequence variation at positions 5'12/3'11 C_LI

microbiology↗

bioRxiv2025

Recovery of infectious Oz virus from cloned cDNA

Oz virus (OZV) is a tick-borne, six-segmented, negative-strand RNA virus in the genus Thogotovirus, family Orthomyxoviridae. A fatal human infection was reported in Japan in 2023. In this study, we established a reverse genetics system to generate infectious recombinant OZV. Six plasmids encoding the full-length OZV genome segments under a murine RNA polymerase I promoter, together with four plasmids expressing viral proteins essential for polymerase activity, were co-transfected into murine cells. This approach enabled efficient recovery of infectious OZV. The recovered recombinant virus exhibited replication kinetics comparable to wild-type OZV. This system provides a platform for molecular studies of OZV.

microbiology↗

bioRxiv2025

MHC Class I-like Gene in Squirrel Monkey Cytomegalovirus and the Evolution of the Virus

Homology searches between viral and human peptides revealed that the S9 protein of squirrel monkey cytomegalovirus (Saimiriine herpesvirus 4 strain [SBHV4]) shares 60.6% amino acid identity across 86.3% of full-length human HLA-A. This represents the most extensive and highest degree of homology reported to date between a viral protein and an MHC class I molecule. Phylogenetic analysis of MHC class I-like DNA sequences from primate HLA-A orthologs and SBHV4-S9 gene suggested that SBHV4-S9 was likely acquired via LINE-1-mediated horizontal gene transfer from the African Old World monkey Piliocolobus tephrosceles or a close ancestor 1.63-6.02 million years ago. SBHV4-S9 appeared to have undergone purifying selection following divergence from P. tephrosceles. Furthermore, phylogenetic analysis of the SBHV4-S1 gene and primate SLAMF6-like genes suggested that this gene was acquired after divergence from a close ancestor of the New World monkeys Saimiri oerstedii and Saimiri sciureus. Comprehensive evaluation of the similarity between eight SBHV4 genes (including S1 and S9) and their respective homologs in 241 primate species, assessed via PCA-syncmer-based Wasserstein distances, revealed that the overall relatedness between SBHV4 and African Cercopithecus ascanius, Cercopithecus pogonias, and Allenopithecus nigroviridis, respectively was significantly greater (i.e., exhibited shorter Wasserstein distances) in each case than that observed with all examined members of the genus Saimiri and Piliocolobus tephrosceles. Collectively, these findings indicate that SBHV4, although isolated from Saimiri sciureus in South America, appears to have a historical connection with Old World monkeys in Africa, despite the typically high host specificity of cytomegaloviruses.

microbiology↗

bioRxiv2024

Entomopoxvirus-like long DNA sequences in human centromeric and peri-centromeric regions

Mammalian genomes harbor a range of endogenous virus-like sequences, although these sequences are typically affected by mutations and deletions, and no examples have been reported of long, conserved regions extending tens of kilobases or more. In this study, a comprehensive similarity search against the complete human T2T genome (hT2T) using high-quality viral genome data was performed. Among nearly continuous viral sequences, the longest identified was Entomopoxvirus, spanning 140 kb with a similarity of over 57%. Notably, Entomopoxvirus-like sequences stood out within the human genome, with a total of 2.42 Mb exhibiting similarity to human sequences. Seven Entomopoxvirus species were fragmented into regions less than 40 kb each, with nearly all of these segments scattered throughout the human genome. Surprisingly, nearly all of these sequences were localized within the hsat1A regions of human centromeric and pericentromeric areas. On chromosome 3, for example, all sequences were confined within the centromere, and extensive transcription was observed across these regions. While the lack of fully sequenced genomes with solid annotations for other eukaryotic species limits our ability to infer the phylogenetic significance of these regions, our findings reveal remarkably long virus-like sequences within centromeric and related regions--as integral components of eukaryotic chromosomes.

bioinformatics↗

bioRxiv2022

FDA-approved drug screening identified micafungin as an antiviral agent against bat-borne emerging zoonotic Pteropine orthoreovirus

Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, severe acute respiratory syndrome (SARS) coronavirus, and SARS-CoV-2. Pteropine orthoreovirus (PRV), which spillover event occurred from fruit bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is a critical tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic effects on cultured Vero cells. Real-time quantitative PCR analysis revealed that six of eight hit compounds significantly inhibited PRV replication. Among them, micafungin used clinically as an antifungal drug, displayed a prominent antiviral effect on PRV. HighlightsO_LIA library of 2,943 FDA-approved drugs was screened to find potential antiviral drugs of Pteropine orthoreovirus. C_LIO_LISix hit compounds dramatically inhibited viral replication in vitro. C_LIO_LIMicafungin possessed antiviral activity to multiple strains of PRV. C_LI

pharmacology and toxicology↗

bioRxiv2022

A comprehensive list of the replication promoters of Bunyavirales reveals a unique promoter structure in Nairoviridae differing from other virus families

Bunyaviruses belong to the order Bunyavirales, the largest group of RNA viruses. They infect a wide variety of host species around the world, including plants, animals and humans, and pose a major threat to public health. Major families in the order Bunyavirales have tri-segmented negative-sense RNA genomes, the 5 and 3 ends of which form complementary strands that serve as a replication promoter. Elucidation of the mechanisms by which viral RNA-dependent RNA polymerase recognizes the promoter to initiates RNA synthesis is important for understanding viral replication and pathogenesis, and for developing antivirals. A list of replication promoter configuration patterns may provide details on the differences in the replication mechanisms among bunyaviruses. Here, by using public sequence data of all known bunyavirus species, we constructed a comprehensive list of the replication promoters comprising 40 nucleotides in both the 5 and 3 ends of the genome that form a specific complementary strand. We showed that among tri-segmented bunyaviruses, viruses belonging to the family Nairoviridae, including the highly pathogenic Crimean-Congo hemorrhagic fever virus, have evolved a GC-rich promoter structure that differs from that of other bunyaviruses. The unique promoter structure might be related to the large genome size of the family Nairoviridae among bunyaviruses. It is possible that the large genome architecture confers a pathogenic advantage. The promoter list provided in this report is expected to be useful for predicting virus family-specific replication mechanisms of segmented negative-sense RNA viruses.

microbiology↗

bioRxiv2022

Frequency of a nucleotide overhang at the 5' end of hemorrhagic fever mammarenavirus genomes in public sequence data

Mammarenaviruses, such as Lassa virus and South American hemorrhagic fever (SAHF) virus, cause severe hemorrhagic fevers in humans, and pose major threats to public health. Mammarenaviruses consist of a bi-segmented negative-sense RNA genome in which the 5 and 3 ends form complementary strands that serve as a replication promoter. Some mammarenaviruses have a nucleotide overhang at the 5 genome end. By examining the complementarity of 5 and 3 genome ends using public mammarenavirus genome sequences, we found that the 5 guanine overhang (5-G overhang) was present more frequently in Lassa and SAHF viruses than in other viruses. The 5-G overhang in the Lassa and SAHF virus sequences was found to be restricted to the L and S segments, respectively. If the genome end sequence data in the public database are accurate, the 5-G overhang may be related to the high pathogenicity of mammarenaviruses in humans.

microbiology↗

bioRxiv2020

Heritable endogenization of an RNA virus in a mammalian species

Viruses are considered one of the driving forces for genome rearrangements via infection and endogenization into the host genome (Kazazian, 2004; Maksakova et al., 2006). In 2010, Horie and colleagues demonstrated that a non-retroviral RNA virus, Borna disease virus (BDV), could integrate into the genome in cultured somatic cells (Horie et al., 2010). However, germline transmission of viral-derived sequences using animal models is yet to be experimentally demonstrated. In this study, we reported a case of heritable endogenization using the encephalomyocarditis virus (EMCV) and laboratory mice. The EMCV is a small non-enveloped single-strand RNA virus without its own reverse transcriptase activity (Carocci et al., 2012). Here, we demonstrated that the EMCV genomic RNA was reverse transcribed into DNA fragments in the murine testes. The DNA sequence originated from the RNA genome of EMCV was also detected in the liver and earlobes of the offspring generated from the EMCV-infected father. This suggests that the exogenous sequence derived from the EMCV is transmitted into the host germline and inherited across subsequent generations. This first experimental demonstration of viral endogenization proposes reconsideration about the impact of viruses as a driving force for genome modification.

genetics↗