Evolutionarily Conserved Interaction between the Phosphoproteins and X Proteins of Bornaviruses from Different Vertebrate Species.

Bornavirus, a non-segmented, negative-strand RNA viruses, is currently classified into several genetically distinct genotypes, such as Borna disease virus (BDV) and avian bornaviruses (ABVs). Recent studies revealed that bornavirus genotypes show unique sequence variability in the putative 5' untranslated region (5' UTR) of X/P mRNA, a bicistronic mRNA for the X protein and phosphoprotein (P). In this study, to understand the evolutionary relationship among the bornavirus genotypes, we investigated the functional interaction between the X and P proteins of four bornavirus genotypes, BDV, ABV genotype 4 and 5 and reptile bornavirus (RBV), the putative 5' UTRs of which exhibit variation in the length. Immunofluorescence and immunoprecipitation analyses using mammalian and avian cell lines revealed that the X proteins of bornaviruses conserve the ability to facilitate the export of P from the nucleus to the cytoplasm via interaction with P. Furthermore, we showed that inter-genotypic interactions may occur between X and P among the genotypes, except for X of RBV. In addition, a BDV minireplicon assay demonstrated that the X and P proteins of ABVs, but not RBV, can affect the polymerase activity of BDV. This study demonstrates that bornaviruses may have conserved the fundamental function of a regulatory protein during their evolution, whereas RBV has evolved distinctly from the other bornavirus genotypes

Novel nanorod precipitate formation in neodymium and titanium codoped bismuth ferrite

The discovery of unusual nanorod precipitates in bismuth ferrite doped with Nd and Ti is reported. The atomic structure and chemistry of the nanorods are determined using a combination of high angle annular dark field imaging, electron energy loss spectroscopy, and density functional calculations. It is found that the structure of the BiFeO3 matrix is strongly modified adjacent to the precipitates; the readiness of BiFeO3 to adopt different structural allotropes in turn explains why such a large axial ratio, uncommon in precipitates, is stabilized. In addition, a correlation is found between the alignment of the rods and the orientation of ferroelastic domains in the matrix, which is consistent with the system's attempt to minimize its internal strain. Density functional calculations indicate a finite density of electronic states at the Fermi energy within the rods, suggesting enhanced electrical conductivity along the rod axes, and motivating future investigations of nanorod functionalities

Bornavirus closely associates and segregates with host chromosomes to ensure persistent intranuclear infection.

Bornaviruses are nonsegmented negative-strand RNA viruses that establish a persistent infection in the nucleus and occasionally integrate a DNA genome copy into the host chromosomal DNA. However, how these viruses achieve intranuclear infection remains unclear. We show that Borna disease virus (BDV), a mammalian bornavirus, closely associates with the cellular chromosome to ensure intranuclear infection. BDV generates viral factories within the nucleus using host chromatin as a scaffold. In addition, the viral ribonucleoprotein (RNP) interacts directly with the host chromosome throughout the cell cycle, using core histones as a docking platform. HMGB1, a host chromatin-remodeling DNA architectural protein, is required to stabilize RNP on chromosomes and for efficient BDV RNA transcription in the nucleus. During metaphase, the association of RNP with mitotic chromosomes allows the viral RNA to segregate into daughter cells and ensure persistent infection. Thus, bornaviruses likely evolved a chromosome-dependent life cycle to achieve stable intranuclear infection

The effect of substrate clamping on the paraelectric to antiferroelectric phase transition in Nd-doped BiFeO₃ thin films

Thin films were deposited on Pt/Ti/SiO₂/Si substrates using pulsed laser deposition from a target with a composition (Bi₀.₈₂₅Nd₀.₁₇₅Fe₀.₉₇Ti₀.₀₃O₃) with 5 mol% excess Bi₂O₃ within the antiferroelectric (AFE) region of the NdFeO₃-BiFeO₃ phase diagram. However, Raman spectroscopy and transmission electron microscopy (TEM) revealed that films consisted of a mosaic microstructure in which (AFE), ferroelectric (FE) and paraelectric (PE) phases coexisted. Variation in the spatial distribution of Nd is typically greater in bulk ceramics than in thin films and therefore, the absence of single phase AFE cannot be attributed to local changes in composition. Instead, it is proposed that clamping due to mismatch in thermal expansion coefficient with the substrate suppresses the large volume change associated with the PE-FE and PE-AFE transition in bulk and its absence in the thin film prevents an avalanche-like transition throughout grains, which in bulk sustains single phase AFE, irrespective of local deviations in the Nd concentration

An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus

Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp

Temperature dependent piezoelectric response and strain–electric-field hysteresis of rare-earth modified bismuth ferrite ceramics

The rare-earth (RE)-modified bismuth ferrite (BiFeO3 or BFO) family of ferroelectrics have uncomplicated lead-free chemistries and simple perovskite structures. Due to the high Curie transition temperature of the parent BiFeO3 perovskite (∼830 °C), they are promising piezoelectric materials for use at elevated temperatures. However, the influence of the specific RE species on the electromechanical behavior at high temperatures and above the coercive electric-field is not widely reported. Here, structural analysis over multiple length scales using X-ray diffraction, transmission electron microscopy and piezoresponse force microscopy is coupled with a high electric-field cycling study and in situ converse d33 measurements up to 325 °C for three RE–BFO ceramic compositions, Bi0.86Sm0.14FeO3, Bi0.88Gd0.12FeO3 and Bi0.91Dy0.09FeO3. The ceramics exhibit different phase assemblages with varying amounts of polar rhombohedral R3c and intermediate antipolar orthorhombic Pbam phases as a function of the RE species. During electric-field cycling at electric-fields with amplitudes of 160 kV cm−1, peak-to-peak strains of 0.23–0.27% are reached for all three compositions. However, there are qualitative differences in the field-induced strain and electric current behavior as a function of electric-field cycling and the materials exhibit an electrical-history dependent behavior. Bi0.91Dy0.09FeO3 possesses an improved d33 stability as a function of temperature relative to the parent BFO perovskite and the highest depolarization temperature among the three RE–BFO compositions, with a stable d33 of ∼22 pC N−1 up to 325 °C

Inhibition of Borna disease virus replication by an endogenous bornavirus-like element in the ground squirrel genome.

Animal genomes contain endogenous viral sequences, such as endogenous retroviruses and retrotransposons. Recently, we and others discovered that nonretroviral viruses also have been endogenized in many vertebrate genomes. Bornaviruses belong to the Mononegavirales and have left endogenous fragments, called "endogenous bornavirus-like elements" (EBLs), in the genomes of many mammals. The striking features of EBLs are that they contain relatively long ORFs which have high sequence homology to the extant bornavirus proteins. Furthermore, some EBLs derived from bornavirus nucleoprotein (EBLNs) have been shown to be transcribed as mRNA and probably are translated into proteins. These features lead us to speculate that EBLs may function as cellular coopted genes. An EBLN element in the genome of the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), itEBLN, encodes an ORF with 77% amino acid sequence identity to the current bornavirus nucleoprotein. In this study, we cloned itEBLN from the ground squirrel genome and investigated its involvement in Borna disease virus (BDV) replication. Interestingly, itEBLN, but not a human EBLN, colocalized with the viral factory in the nucleus and appeared to affect BDV polymerase activity by being incorporated into the viral ribonucleoprotein. Our data show that, as do certain endogenous retroviruses, itEBLN potentially may inhibit infection by related exogenous viruses in vivo

Borna disease virus possesses an NF-ĸB inhibitory sequence in the nucleoprotein gene.

Borna disease virus (BDV) has a non-segmented, negative-stranded RNA genome and causes persistent infection in many animal species. Previous study has shown that the activation of the IκB kinase (IKK)/NF-κB pathway is reduced by BDV infection even in cells expressing constitutively active mutant IKK. This result suggests that BDV directly interferes with the IKK/NF-κB pathway. To elucidate the mechanism for the inhibition of NF-κB activation by BDV infection, we evaluated the cross-talk between BDV infection and the NF-κB pathway. Using Multiple EM for Motif Elicitation analysis, we found that the nucleoproteins of BDV (BDV-N) and NF-κB1 share a common ankyrin-like motif. When THP1-CD14 cells were pre-treated with the identified peptide, NF-κB activation by Toll-like receptor ligands was suppressed. The 20S proteasome assay showed that BDV-N and BDV-N-derived peptide inhibited the processing of NF-κB1 p105 into p50. Furthermore, immunoprecipitation assays showed that BDV-N interacted with NF-κB1 but not with NF-κB2, which shares no common motif with BDV-N. These results suggest BDV-N inhibits NF-κB1 processing by the 20S proteasome through its ankyrin-like peptide sequence, resulting in the suppression of IKK/NF-κB pathway activation. This inhibitory effect of BDV on the induction of the host innate immunity might provide benefits against persistent BDV infection

Gallus gallus coxsackievirus and adenovirus receptor facilitates the binding of fowl adenovirus serotype 1 in chickens

Coxsackievirus and adenovirus receptor (CXADR) is an integral membrane protein that serves as a receptor for coxsackie B viruses and adenovirus types 2 and 5. Previous studies demonstrated that Fowl adenovirus (FAV) can also utilize Homo sapiens CXADR to infect cells. FAV is a double-stranded DNA virus of the family Adenoviridae. FAV causes inclusion body hepatitis and hydropericardium syndrome in chickens. In addition, FAV serotypes 1 and 8 have recently been shown to cause gizzard erosion in chickens. These chicken diseases and growth insufficiency caused by FAV infection result in great economic loss. Thus, identifying and characterizing the viral receptor would further enhance our understanding of the mechanisms underlying virus infection and histocompatibility. Here, in order to determine the FAV receptor in chickens, we investigated the effect of the recently identified Gallus gallus CXADR (ggCXADR) on FAV infection. Overexpression of ggCXADR in CHO cells resulted in increased FAV binding and expression of early FAV genes. However, the propagation of infectious viruses in CHO cells expressing ggCXADR was not detected. These findings provide the basis for further studies aimed at elucidating the infection mechanism of FAV. Further research is required to characterize the additional host factors involved in FAV infection and life cycle