Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study.

A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses.

Investigating mobile element variations by statistical genetics.

The integration of structural variations (SVs) in statistical genetics provides an opportunity to understand the genetic factors influencing complex human traits and disease. Recent advances in long-read technology and variant calling methods for short reads have improved the accurate discovery and genotyping of SVs, enabling their use in expression quantitative trait loci (eQTL) analysis and genome-wide association studies (GWAS). Mobile elements are DNA sequences that insert themselves into various genome locations.

Phylogenetic analysis of the promoter element 2 of paramyxo- and filoviruses.

Unlabelled: Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the "rule of six." However, our knowledge of PE2 has been limited to a narrow spectrum of virus species.

Mobile element variation contributes to population-specific genome diversification, gene regulation and disease risk.

Mobile genetic elements (MEs) are heritable mutagens that recursively generate structural variants (SVs). ME variants (MEVs) are difficult to genotype and integrate in statistical genetics, obscuring their impact on genome diversification and traits. We developed a tool that accurately genotypes MEVs using short-read whole-genome sequencing (WGS) and applied it to global human populations.

Variant spectrum of von Hippel-Lindau disease and its genomic heterogeneity in Japan.

Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases.

Wall teichoic acid-dependent phagocytosis of intact cell walls of elicits IL-12 secretion from macrophages.

Selected lactic acid bacteria can stimulate macrophages and dendritic cells to secrete IL-12, which plays a key role in activating innate and cellular immunity. In this study, we investigated the roles of cell wall teichoic acids (WTAs) displayed on whole intact cell walls (ICWs) of in activation of mouse macrophages. ICWs were prepared from whole bacterial cells of several lactobacilli without physical disruption, and thus retaining the overall shapes of the bacteria.

Preparation of Non-overlapping Transposable Elements (TEs) Annotation by Interval Tree.

Transposable elements (TEs) are a major source of PIWI-interacting RNAs (piRNAs), therefore properly assigning piRNA library sequencing reads to the TEs from which they were derived is important for accurate assessment of piRNA biology. When calculating the abundance of small RNA-seq reads mapping to various TEs, a non-overlapping TE annotation is preferable because reads mapping to more than one genomic feature will often be excluded when counting reads. However, most unmodified TE annotations contain some degree of overlap between TE features.

A hominoid-specific endogenous retrovirus may have rewired the gene regulatory network shared between primordial germ cells and naïve pluripotent cells.

Mammalian germ cells stem from primordial germ cells (PGCs). Although the gene regulatory network controlling the development of germ cells such as PGCs is critical for ensuring gamete integrity, substantial differences exist in this network among mammalian species, suggesting that this network has been modified during mammalian evolution. Here, we show that a hominoid-specific group of endogenous retroviruses, LTR5_Hs, discloses enhancer-like signatures in human in vitro-induced PGCs, PGC-like cells (PGCLCs).

An endogenous bornavirus-like nucleoprotein in miniopterid bats retains the RNA-binding properties of the original viral protein.

Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences derived from bornaviral N genes in vertebrate genomes. Some EBLNs have been suggested to encode functional proteins in host cells; however, little is known about their evolution and functional relationship to the viral genes from which EBLNs originate. Here, we predicted functionality of EBLNs based on the properties of N as an RNA-binding protein.

Hidden Viral Sequences in Public Sequencing Data and Warning for Future Emerging Diseases.

RNA viruses cause numerous emerging diseases, mostly due to transmission from mammalian and avian reservoirs. Large-scale surveillance of RNA viral infections in these animals is a fundamental step for controlling viral infectious diseases. Metagenomic analysis is a powerful method for virus identification with low bias and has contributed substantially to the discovery of novel viruses.

BUD23-TRMT112 interacts with the L protein of Borna disease virus and mediates the chromosomal tethering of viral ribonucleoproteins.

Persistent intranuclear infection is an uncommon infection strategy among RNA viruses. However, Borna disease virus 1 (BoDV-1), a nonsegmented, negative-strand RNA virus, maintains viral infection in the cell nucleus by forming structured aggregates of viral ribonucleoproteins (vRNPs), and by tethering these vRNPs onto the host chromosomes. To better understand the nuclear infection strategy of BoDV-1, we determined the host protein interactors of the BoDV-1 large (L) protein.

100-My history of bornavirus infections hidden in vertebrate genomes.

Although viruses have threatened our ancestors for millions of years, prehistoric epidemics of viruses are largely unknown. Endogenous bornavirus-like elements (EBLs) are ancient bornavirus sequences derived from the viral messenger RNAs that were reverse transcribed and inserted into animal genomes, most likely by retrotransposons. These elements can be used as molecular fossil records to trace past bornaviral infections.

A Human Endogenous Bornavirus-Like Nucleoprotein Encodes a Mitochondrial Protein Associated with Cell Viability.

Endogenous retroviruses (ERVs) are sequences in animal genomes that originated from ancient retrovirus infections; they provide genetic novelty in hosts by being coopted as functional genes or elements during evolution. Recently, we demonstrated that endogenous elements from not only from retroviruses but also nonretroviral RNA viruses are a possible source of functional genes in host animals. The remnants of ancient bornavirus infections, called endogenous bornavirus-like elements (EBLs), are present in the genomes of a wide variety of vertebrate species, and some express functional products in host cells.

Virus-derived variation in diverse human genomes.

Acquisition of genetic material from viruses by their hosts can generate inter-host structural genome variation. We developed computational tools enabling us to study virus-derived structural variants (SVs) in population-scale whole genome sequencing (WGS) datasets and applied them to 3,332 humans. Although SVs had already been cataloged in these subjects, we found previously-overlooked virus-derived SVs.

Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution.

Hepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here, we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance.

Virus-like insertions with sequence signatures similar to those of endogenous nonretroviral RNA viruses in the human genome.

Understanding the genetics and taxonomy of ancient viruses will give us great insights into not only the origin and evolution of viruses but also how viral infections played roles in our evolution. Endogenous viruses are remnants of ancient viral infections and are thought to retain the genetic characteristics of viruses from ancient times. In this study, we used machine learning of endogenous RNA virus sequence signatures to identify viruses in the human genome that have not been detected or are already extinct.

Effect of Spacer Length in Pyrene-Modified-Phenylboronic Acid Probe/CyD Complexes on Fluorescence-based Recognition of Monosaccharides in Aqueous Solution.

The chemical sensing of saccharides is of importance for the diagnosis of diabetes. Various enzymatic sensors have been developed, but their heat and pH instability issues need to be resolved. In this regard, the development of artificial saccharide sensors with high stability is attracting attention.

Endogenous retroviruses drive species-specific germline transcriptomes in mammals.

Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species and speciation. Male germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition and have been subject to evolutionary divergence among mammals. However, the mechanisms underlying germline regulatory divergence remain undetermined.

ADAR2 Is Involved in Self and Nonself Recognition of Borna Disease Virus Genomic RNA in the Nucleus.

Cells sense pathogen-derived double-stranded RNA (dsRNA) as nonself. To avoid autoimmune activation by self dsRNA, cells utilize A-to-I editing by adenosine deaminase acting on RNA 1 (ADAR1) to disrupt dsRNA structures. Considering that viruses have evolved to exploit host machinery, A-to-I editing could benefit innate immune evasion by viruses.

In vitro activation and maturation of human mononuclear phagocytes by stimulation with liposomes coated with a neoglycolipid containing α1-3, α1-6-mannotriose.

In this study, we assessed the potential of liposomes coated with a neoglycolipid containing α1-3,α1-6-mannotriose residues (Man3-DPPE; Manα1-6(Manα1-3)Manitol-DPPE) for in vitro activation and maturation of human mononuclear phagocytes. In response to treatment with Man3-DPPE-coated liposomes (Man3-OMLs), PMA-stimulated human THP-1 cells showed enhanced expression of CD40, CD80 and HLA-DR and secreted significant levels of IL-12p40. Among various linkages of Man2-DPPE-coated liposomes, only liposomes coated with Manα1-6Manitol-DPPE (α1-6Man2-DPPE) induced these cellular responses similarly to Man3-OML treatment.

Splicing-Dependent Subcellular Targeting of Borna Disease Virus Nucleoprotein Isoforms.

Targeting of viral proteins to specific subcellular compartments is a fundamental step for viruses to achieve successful replication in infected cells. Borna disease virus 1 (BoDV-1), a nonsegmented, negative-strand RNA virus, uniquely replicates and persists in the cell nucleus. Here, it is demonstrated that BoDV nucleoprotein (N) transcripts undergo mRNA splicing to generate truncated isoforms.

Linkage between the leader sequence and leader RNA production in Borna disease virus-infected cells.

The 3'-untranslated region (UTR) of the non-segmented, negative-strand (NNS) RNA viral genome is called the leader sequence, and functions as the promoter for viral replication and transcription. NNS RNA viruses also use the sequence as a template to synthesize leader RNAs (leRNAs) with unknown functions. Borna disease virus (BDV) is unique because it establishes a persistent infection and replicates in the nucleus.