Evolutionary maintenance of filovirus-like genes in bat genomes

<p>Abstract</p> <p>Background</p> <p>Little is known of the biological significance and evolutionary maintenance of integrated non-retroviral RNA virus genes in eukaryotic host genomes. Here, we isolated novel filovirus-like genes from bat genomes and tested for evolutionary maintenance. We also estimated the age of filovirus VP35-like gene integrations and tested the phylogenetic hypotheses that there is a eutherian mammal clade and a marsupial/ebolavirus/Marburgvirus dichotomy for filoviruses.</p> <p>Results</p> <p>We detected homologous copies of VP35-like and NP-like gene integrations in both Old World and New World species of <it>Myotis </it>(bats). We also detected previously unknown VP35-like genes in rodents that are positionally homologous. Comprehensive phylogenetic estimates for filovirus NP-like and VP35-like loci support two main clades with a marsupial and a rodent grouping within the ebolavirus/Lloviu virus/Marburgvirus clade. The concordance of VP35-like, NP-like and mitochondrial gene trees with the expected species tree supports the notion that the copies we examined are orthologs that predate the global spread and radiation of the genus <it>Myotis</it>. Parametric simulations were consistent with selective maintenance for the open reading frame (ORF) of VP35-like genes in <it>Myotis</it>. The ORF of the filovirus-like VP35 gene has been maintained in bat genomes for an estimated 13. 4 MY. ORFs were disrupted for the NP-like genes in <it>Myotis</it>. Likelihood ratio tests revealed that a model that accommodates positive selection is a significantly better fit to the data than a model that does not allow for positive selection for VP35-like sequences. Moreover, site-by-site analysis of selection using two methods indicated at least 25 sites in the VP35-like alignment are under positive selection in <it>Myotis</it>.</p> <p>Conclusions</p> <p>Our results indicate that filovirus-like elements have significance beyond genomic imprints of prior infection. That is, there appears to be, or have been, functionally maintained copies of such genes in mammals. "Living fossils" of filoviruses appear to be selectively maintained in a diverse mammalian genus (<it>Myotis</it>).</p

Virus-host co-evolution under a modified nuclear genetic code

Among eukaryotes with modified nuclear genetic codes, viruses are unknown. However, here we provide evidence of an RNA virus that infects a fungal host (Scheffersomyces segobiensis) with a derived nuclear genetic code where CUG codes for serine. The genomic architecture and phylogeny are consistent with infection by a double-stranded RNA virus of the genus Totivirus. We provide evidence of past or present infection with totiviruses in five species of yeasts with modified genetic codes. All but one of the CUG codons in the viral genome have been eliminated, suggesting that avoidance of the modified codon was important to viral adaptation. Our mass spectroscopy analysis indicates that a congener of the host species has co-opted and expresses a capsid gene from totiviruses as a cellular protein. Viral avoidance of the host’s modified codon and host co-option of a protein from totiviruses suggest that RNA viruses co-evolved with yeasts that underwent a major evolutionary transition from the standard genetic code

Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia

Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4lps-d), mice deficient in TLR9 (TLR9−/−) and TLR4/9 double mutant mice (TLR4lps-d/TLR9−/−) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4lps-d/TLR9−/− double mutant mice. Early lung expression of TNF-α, IL-12, and chemokines was TLR4 dependent, while IFN-γ production and the later expression of TNF-α and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4lps-d/TLR9−/− double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response

2022 taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales

In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.Instituto de Patología VegetalFil: Kuhn, Jens H. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Integrated Research Facility at Fort Detrick; Estados UnidosFil: Adkins, Scott. US Horticultural Research Laboratory. United States Department of Agriculture. Agricultural Research Service; Estados UnidosFil: Alkhovsky, Sergey V. Ministry of Health of Russian Federation. National Center on Epidemiology and Microbiology .D.I. Ivanovsky Institute of Virology of N.F. Gamaleya; RusiaFil: Avšič-Županc, Tatjana. University of Ljubljana. Faculty of Medicine. Institute of Microbiology and Immunology; EsloveniaFil: Ayllón, María A. Universidad Politécnica de Madrid. Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria.Centro de Biotecnología y Genómica de Plantas; EspañaFil: Ayllón, María A. Universidad Politécnica de Madrid. Escuela Técnica Superior de Ingeniería Agronómica, Alimentaria y de Biosistemas. Departamento de Biotecnología-Biología Vegetal; EspañaFil: Bahl, Justin. University of Georgia. Center for Ecology of Infectious Diseases. Insitute of Bioinformatics. Department of Infectious Diseases. Department of Epidemiology and Biostatistics; Estados UnidosFil: Balkema-Buschmann, Anne. Friedrich-Loeffler-Institut. Institute of Novel and Emerging Infectious Diseases; AlemaniaFil: Ballinger, Matthew J. Mississippi State University. Department of Biological Sciences; Estados UnidosFil: Bandte, Martina. Humboldt-Universität zu Berlin. Faculty of Life Sciences. Division Phytomedicine; AlemaniaFil: Beer, Martin. Friedrich-Loeffler-Institut. Institute of Diagnostic Virology; AlemaniaFil: Bejerman, Nicolas Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Bejerman, Nicolas Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); ArgentinaFil: Lodden Økland, Arnfnn. Pharmaq Analytiq; Norueg

Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells

The WiggleZ Dark Energy Survey: measuring the cosmic expansion history using the Alcock-Paczynski test and distant supernovae

Astronomical observations suggest that today's Universe is dominated by a dark energy of unknown physical origin. One of the most notable consequences in many models is that dark energy should cause the expansion of the Universe to accelerate: but the expansion rate as a function of time has proven very difficult to measure directly. We present a new determination of the cosmic expansion history by combining distant supernovae observations with a geometrical analysis of large-scale galaxy clustering within the WiggleZ Dark Energy Survey, using the Alcock-Paczynski test to measure the distortion of standard spheres. Our result constitutes a robust and non-parametric measurement of the Hubble expansion rate as a function of time, which we measure with 10-15% precision in four bins within the redshift range 0.1 < z < 0.9. We demonstrate that the cosmic expansion is accelerating, in a manner independent of the parameterization of the cosmological model (although assuming cosmic homogeneity in our data analysis). Furthermore, we find that this expansion history is consistent with a cosmological-constant dark energy.Comment: 13 pages, 7 figures, accepted for publication by MNRA

Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

INTRODUCTION: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma. METHODS: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene. RESULTS: Genetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07-2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44-4.19, P = 9.5 ×10-04). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96-1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03-1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma. CONCLUSION: A genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis

The WiggleZ Dark Energy Survey: Joint measurements of the expansion and growth history at z < 1

We perform a joint determination of the distance-redshift relation and cosmic expansion rate at redshifts z = 0.44, 0.6 and 0.73 by combining measurements of the baryon acoustic peak and Alcock-Paczynski distortion from galaxy clustering in the WiggleZ Dark Energy Survey, using a large ensemble of mock catalogues to calculate the covariance between the measurements. We find that D_A(z) = (1205 +/- 114, 1380 +/- 95, 1534 +/- 107) Mpc and H(z) = (82.6 +/- 7.8, 87.9 +/- 6.1, 97.3 +/- 7.0) km/s/Mpc at these three redshifts. Further combining our results with other baryon acoustic oscillation and distant supernovae datasets, we use a Monte Carlo Markov Chain technique to determine the evolution of the Hubble parameter H(z) as a stepwise function in 9 redshift bins of width dz = 0.1, also marginalizing over the spatial curvature. Our measurements of H(z), which have precision better than 7% in most redshift bins, are consistent with the expansion history predicted by a cosmological-constant dark-energy model, in which the expansion rate accelerates at redshift z < 0.7.Comment: 11 pages, 11 figures, accepted for publication in MNRA

Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

Taxonomy of the order Bunyavirales : second update 2018

In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).Non peer reviewe