A phylogenomic analysis of Marek's disease virus reveals independent paths to virulence in Eurasia and North America

Virulence determines the impact a pathogen has on the fitness of its host, yet current understanding of the evolutionary origins and causes of virulence of many pathogens is surprisingly incomplete. Here, we explore the evolution of Marek's disease virus (MDV), a herpesvirus commonly afflicting chickens and rarely other avian species. The history of MDV in the 20th century represents an important case study in the evolution of virulence. The severity of MDV infection in chickens has been rising steadily since the adoption of intensive farming techniques and vaccination programs in the 1950s and 1970s, respectively. It has remained uncertain, however, which of these factors is causally more responsible for the observed increase in virulence of circulating viruses. We conducted a phylogenomic study to understand the evolution of MDV in the context of dramatic changes to poultry farming and disease control. Our analysis reveals evidence of geographical structuring of MDV strains, with reconstructions supporting the emergence of virulent viruses independently in North America and Eurasia. Of note, the emergence of virulent viruses appears to coincide approximately with the introduction of comprehensive vaccination on both continents. The time-dated phylogeny also indicated that MDV has a mean evolutionary rate of ~1.6 × 10−5 substitutions per site per year. An examination of gene-linked mutations did not identify a strong association between mutational variation and virulence phenotypes, indicating that MDV may evolve readily and rapidly under strong selective pressures and that multiple genotypic pathways may underlie virulence adaptation in MDV

Invasive mammal eradication on islands results in substantial conservation gains

More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List—6% of all these highly threatened species—likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna.This is the publisher’s final pdf. The published article is copyrighted by the National Academy of Sciences and can be found at: http://www.pnas.org/Keywords: island, restoration, invasive species, conservation, eradicationKeywords: island, restoration, invasive species, conservation, eradicatio

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Construction and Characterization of a Recombinant Herpes Simplex Virus Type 1 Which Overexpresses the Transrepressor Protein ICP0R

AbstractICP0R is a truncated form of the herpes simplex virus type 1 (HSV-1) transactivator protein ICP0 that is synthesized at low levels during infection through an alternative splicing mechanism. In transient expression assays, ICP0R has been shown to inhibit the transactivation function of several HSV-1 regulatory proteins, suggesting that an antiviral strategy which alters normal ICP0 mRNA splicing and thereby stimulates the synthesis of ICP0R protein may have potential in suppressing HSV-1 infections. To explore the feasibility of this approach, a recombinant virus was constructed which expressed high levels of ICP0R instead of ICP0. Surprisingly, overexpression of the ICP0R protein in this virus, HSV-KST, had no detectable effect on virus replication, since the growth properties of HSV-KST were indistinguishable from those of the ICP0/ICP0R null mutant dl1403, and HSV-KST was no more efficient than dl1403 at inhibiting the replication of an ICP0-expressing wild-type virus. The absence of a demonstrable phenotype in HSV-KST was not due to the acquisition of an inactivating mutation in the gene encoding ICP0R, since copies of the gene rescued from this virus retained full transrepression capability in transient expression assays. These results indicate that the ability of ICP0R to act as a transrepressor is significantly reduced if not completely eliminated in the context of a productive HSV-1 infection and suggest that this protein may not represent an exploitable target for the development of novel antiviral therapies

Viral proteogenomic and expression profiling during productive replication of a skin-tropic herpesvirus in the natural host.

Efficient transmission of herpesviruses is essential for dissemination in host populations; however, little is known about the viral genes that mediate transmission, mostly due to a lack of natural virus-host model systems. Marek's disease is a devastating herpesviral disease of chickens caused by Marek's disease virus (MDV) and an excellent natural model to study skin-tropic herpesviruses and transmission. Like varicella zoster virus that causes chicken pox in humans, the only site where infectious cell-free MD virions are efficiently produced is in epithelial skin cells, a requirement for host-to-host transmission. Here, we enriched for heavily infected feather follicle epithelial skin cells of live chickens to measure both viral transcription and protein expression using combined short- and long-read RNA sequencing and LC/MS-MS bottom-up proteomics. Enrichment produced a previously unseen breadth and depth of viral peptide sequencing. We confirmed protein translation for 84 viral genes at high confidence (1% FDR) and correlated relative protein abundance with RNA expression levels. Using a proteogenomic approach, we confirmed translation of most well-characterized spliced viral transcripts and identified a novel, abundant isoform of the 14 kDa transcript family via IsoSeq transcripts, short-read intron-spanning sequencing reads, and a high-quality junction-spanning peptide identification. We identified peptides representing alternative start codon usage in several genes and putative novel microORFs at the 5' ends of two core herpesviral genes, pUL47 and ICP4, along with strong evidence of independent transcription and translation of the capsid scaffold protein pUL26.5. Using a natural animal host model system to examine viral gene expression provides a robust, efficient, and meaningful way of validating results gathered from cell culture systems