[Show abstract][Hide abstract] ABSTRACT: We report here the genome sequence of a circular virus isolated from samples of an Alaskan black-capped chickadee (
) gastrointestinal tract. The genome is 2,152 bp in length and is most similar (30 to 44.5% amino acid identity) to the genome sequences of other single-stranded DNA (ssDNA) circular viruses belonging to the gemycircularvirus group.
[Show abstract][Hide abstract] ABSTRACT: We report the draft genome sequence of Laverivirus UC1, assembled from San Francisco wastewater. This dicistronic RNA virus
bears some similarity to dicistroviruses; however, it appears to have a unique genome organization relative to all other known
[Show abstract][Hide abstract] ABSTRACT: We report here the draft genome sequences of marine RNA phages EC and MB assembled from metagenomic sequencing of organisms
in San Francisco wastewater. These phages showed moderate translated amino acid identity to other enterobacteria phages and
appear to constitute novel members of the Leviviridae family.
[Show abstract][Hide abstract] ABSTRACT: We report the draft genome sequences of ciliovirus and brinovirus, two members of a likely new family of RNA viruses assembled
from San Francisco wastewater. Based on sequence alignments and a nonuniversal genetic code, we believe these to be the first
described RNA viruses of ciliates; however, more work is necessary to confirm their host.
[Show abstract][Hide abstract] ABSTRACT: We report the draft genome sequences of marine RNA viruses SF-1, SF-2, and SF-3, which were assembled from metagenomic sequencing
of organisms in San Francisco wastewater. These viruses were most closely related to marine RNA virus JP-B and algae viruses.
[Show abstract][Hide abstract] ABSTRACT: Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a disease that has caused the deaths of millions of bats in North America. This psychrophilic fungus proliferates at low temperatures and targets hibernating bats, resulting in their premature arousal from stupor with catastrophic consequences. Despite the impact of white-nose syndrome, little is known about the fungus itself or how it infects its mammalian host. P. destructans is not amenable to genetic manipulation, and therefore understanding the proteins involved in infection requires alternative approaches. Here, we identify hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased substrate profiling technique to define active peptidases. These experiments revealed that endopeptidases are the major proteolytic activities secreted by P. destructans, and that collagen, the major structural protein in mammals, is actively degraded by the secretome. A serine endopeptidase, hereby-named Destructin-1, was subsequently identified, and a recombinant form overexpressed and purified. Biochemical analysis of Destructin-1 showed that it mediated collagen degradation, and a potent inhibitor of peptidase activity was identified. Treatment of P. destructans-conditioned media with this antagonist blocked collagen degradation and facilitated the detection of additional secreted proteolytic activities, including aminopeptidases and carboxypeptidases. These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host.
Proceedings of the National Academy of Sciences 05/2015; 112(24):201507082. DOI:10.1073/pnas.1507082112 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Until recently, members of the monogeneric family Arenaviridae (arenaviruses) have been known to infect only muroid rodents and, in one case, possibly phyllostomid bats. The paradigm of arenaviruses exclusively infecting small mammals shifted dramatically when several groups independently published the detection and isolation of a divergent group of arenaviruses in captive alethinophidian snakes. Preliminary phylogenetic analyses suggest that these reptilian arenaviruses constitute a sister clade to mammalian arenaviruses. Here, the members of the International Committee on Taxonomy of Viruses (ICTV) Arenaviridae Study Group, together with other experts, outline the taxonomic reorganization of the family Arenaviridae to accommodate reptilian arenaviruses and other recently discovered mammalian arenaviruses and to improve compliance with the Rules of the International Code of Virus Classification and Nomenclature (ICVCN). PAirwise Sequence Comparison (PASC) of arenavirus genomes and NP amino acid pairwise distances support the modification of the present classification. As a result, the current genus Arenavirus is replaced by two genera, Mammarenavirus and Reptarenavirus, which are established to accommodate mammalian and reptilian arenaviruses, respectively, in the same family. The current species landscape among mammalian arenaviruses is upheld, with two new species added for Lunk and Merino Walk viruses and minor corrections to the spelling of some names. The published snake arenaviruses are distributed among three new separate reptarenavirus species. Finally, a non-Latinized binomial species name scheme is adopted for all arenavirus species. In addition, the current virus abbreviations have been evaluated, and some changes are introduced to unequivocally identify each virus in electronic databases, manuscripts, and oral proceedings.
Archives of Virology 05/2015; 160(7):1851–1874. DOI:10.1007/s00705-015-2418-y · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite significant advances in antimalarial chemotherapy over the past 30 years, development of resistance to frontline drugs remains a significant challenge that limits efforts to eradicate the disease. We now report the discovery of a new class of antimalarials, salinipostins A-K, with low nanomolar potencies and high selectivity indices against mammalian cells (salinipostin A: Plasmodium falciparum EC50 50 nM, HEK293T cytotoxicity EC50 > 50 μM). These compounds were isolated from a marine-derived Salinospora sp. bacterium and contain a bicyclic phosphotriester core structure, which is a rare motif among natural products. This scaffold differs significantly from the structures of known antimalarial compounds and represents a new lead structure for the development of therapeutic targets in malaria. Examination of the growth stage specificity of salinipostin A indicates that it exhibits growth stage-specific effects that differ from compounds that inhibit heme polymerization, while resistance selection experiments were unable to identify parasite populations that exhibited significant resistance against this compound class.
The Journal of Organic Chemistry 01/2015; 80(3). DOI:10.1021/jo5024409 · 4.72 Impact Factor