Biology subjects

Evans, M. J.

Publications and source records attributed to Evans, M. J..

At least 19 recordsLinked to original sources

bioRxiv2026

The Hao-Fountain syndrome gene USP7 restricts neurotropic orthoflavivirus entry through cell intrinsic control of endosomal dynamics

Neurodevelopmental disorders are increasingly associated with immune phenotypes, including autoinflammation, immunodeficiency, and increased susceptibility to severe infection. To determine whether neurodevelopmental disorders-associated genes exert immune functions, we performed an arrayed siRNA screen targeting 28 genes with nonredundant cellular roles and assessed their effects on Zika virus (ZIKV) infection and innate immune pathways. We identified hits that intrinsically restrict ZIKV infection and modulate inflammatory pathways following infection. We further characterized the antiviral activity of the Hao-Fountain syndrome gene USP7, which potently restricts selected neurotropic orthoflaviviruses. USP7 inhibits ZIKV internalization before viral membrane fusion and genome release into the cytoplasm. Because USP7 plays a role in endosomal tubulation and recycling, we investigated whether endosomal recycling pathways restrict ZIKV infection. We identified the USP7-regulated E3 ubiquitin ligase TRIM27, as well as the recycling-associated Rab GTPases RAB11 and RAB35, as potent regulators of ZIKV infection. Infection assays using cell lines expressing pathogenic USP7 variants and primary fibroblasts from individuals with Hao-Fountain syndrome demonstrated that disease-associated USP7 mutations impair its antiviral activity and increase permissivity to ZIKV infection. These findings are consistent with recent case reports of unusually severe viral infection during early life in individuals with Hao-Fountain syndrome. Collectively, our study identifies endosomal recycling pathways as important intrinsic restriction mechanisms against neurotropic orthoflaviviruses and nominates pathogenic USP7 variation as a candidate inborn error of immunity.

microbiology↗

bioRxiv2025

Coevolutionary constraints of Zika virus nonstructural protein 5 replication and interferon antagonism activities

The flavivirus nonstructural protein 5 performs multiple functions during infection, including RNA replication and type I interferon signaling antagonism. Although flavivirus NS5 proteins inhibit IFN signaling through distinct mechanisms, which suggests evolutionary flexibility, the evolutionary constraints for these activities to coexist within a single protein remain to be determined. Here, we mapped the Zika virus NS5 STAT2 antagonism determinants and compared them with replication constraints defined by deep mutational scanning. Antagonism and replication determinant extensively overlapped, and no single amino acid substitution eliminated antagonism without impairing replication. Resolving these fitness landscapes in parallel identified specific combinations of partially functional substitutions that retained replication capacity while markedly reducing antagonism. These viruses were profoundly attenuated in human STAT2 knock-in mice. Our results uncover a fundamental evolutionary constraint linking replication and immune evasion activities in NS5, highlight that STAT2 antagonism is essential for ZIKV pathogenesis and provide new avenues for attenuated ZIKV vaccines.

microbiology↗

bioRxiv2025

Construction of a CMV promoter-driven Langat virus cDNA clone and reporter viruses

Langat virus (LGTV) is a tick-borne member of the Flaviviridae family and a biosafety level 2 surrogate for studying tick-borne encephalitis virus (TBEV) replication and pathogenesis. Here, we report the construction of a plasmid encoding a cytomegalovirus (CMV) promoter-driven LGTV cDNA that initiates infection following direct transfection of mammalian cells. Incorporation of three introns eliminated viral cDNA-associated toxicity in bacteria, enabling stable propagation of the full-length plasmid. Transfection of this construct resulted in high-level production of infectious LGTV, which exhibited robust replication kinetics, though slightly slower growth compared to a patient-derived isolate. We further engineered mCherry and Gaussia luciferase reporter versions of the clone, which yielded viruses expressing high levels of their respective reporters while retaining efficient replication. These LGTV infectious clones provide versatile tools for investigating viral replication, gene function, and pathogenesis, and may facilitate screening for antiviral inhibitors. HighlightsO_LISingle-plasmid CMV-driven system launches infectious Langat virus (LGTV) C_LIO_LIThree introns stabilize full-length LGTV cDNA in E. coli C_LIO_LIDNA transfection yields high-titer infectious virus in mammalian cells C_LIO_LIReporter LGTVs enable fluorescent and luminescent infection readouts C_LIO_LIProvides a versatile platform for LGTV genetics and pathogenesis studies C_LI

microbiology↗

bioRxiv2025

A non-vesicular Argonaute protein is transmitted from nematode to mouse and is important for parasite survival

Argonautes are ancient proteins with well-characterised functions in cell-autonomous gene regulation and genome defense but less clear roles in non-cell-autonomous processes. Extracellular Argonautes have been reported across plants, animals and protozoa yet their biochemical and functional properties remain elusive. Here we demonstrate that an extracellular Argonaute (exWAGO) released by the rodent-infective parasitic nematode Heligmosomoides bakeri is detectable inside mouse cells during the natural infection. We further show that exWAGO is released from H.bakeri in both vesicular and non-vesicular forms that have different resistances to proteolysis, different accessibilities to antibodies and associate with different subsets of secondary siRNAs. Using recombinant exWAGO protein we demonstrate that non-vesicular exWAGO is directly internalised by mouse cells in vitro and that immunisation of mice with exWAGO confers partial protection against subsequent H. bakeri infection and generates antibodies that block exWAGO uptake into cells. Finally, we show that properties of exWAGO are conserved across Clade V nematodes that infect humans and livestock. Together this work expands the context in which Argonautes function and illuminates an RNA-binding protein as a vaccine target for parasitic nematodes.

molecular biology↗

bioRxiv2024

Local and global density have distinct and parasite-dependent effects on infection in wild sheep

High density should drive greater parasite exposure. However, evidence linking density with infection generally uses density proxies, rather than of individuals per space within a continuous population. We used a long-term study of wild sheep to link within-population spatiotemporal variation in host density with individual parasite counts. Although four parasites exhibited strong positive relationships with local density, these relationships were mostly restricted to juveniles and faded in adults. Further, one ectoparasite showed strong negative relationships across all age classes. In contrast, population size - a measure of global density - had limited explanatory power, and its effects did not remove those of spatial density, but were complementary. These results indicate that local and global density can exhibit diverse and contrasting effects on infection within populations. Spatial measures of within-population local density may provide substantial additional insight to temporal metrics based on population size, and investigating them more widely could be highly revealing.

ecology↗

bioRxiv2023

The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies

Zika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential. ImportanceThe wide endemic range of mosquito-vectored flaviviruses - such as Zika virus and dengue virus serotypes 1-4 - places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue towards development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.

microbiology↗

bioRxiv2022

Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.

We and others have previously shown that the SARS-CoV-2 accessory protein ORF6 is a powerful antagonist of the interferon (IFN) signaling pathway by directly interacting with Nup98-Rae1 at the nuclear pore complex (NPC) and disrupting bidirectional nucleo-cytoplasmic trafficking. In this study, we further assessed the role of ORF6 during infection using recombinant SARS-CoV-2 viruses carrying either a deletion or a well characterized M58R loss-of-function mutation in ORF6. We show that ORF6 plays a key role in the antagonism of IFN signaling and in viral pathogenesis by interfering with karyopherin(importin)-mediated nuclear import during SARS-CoV-2 infection both in vitro, and in the Syrian golden hamster model in vivo. In addition, we found that ORF6-Nup98 interaction also contributes to inhibition of cellular mRNA export during SARS-CoV-2 infection. As a result, ORF6 expression significantly remodels the host cell proteome upon infection. Importantly, we also unravel a previously unrecognized function of ORF6 in the modulation of viral protein expression, which is independent of its function at the nuclear pore. Lastly, we characterized the ORF6 D61L mutation that recently emerged in Omicron BA.2 and BA.4 and demonstrated that it is able to disrupt ORF6 protein functions at the NPC and to impair SARS-CoV-2 innate immune evasion strategies. Importantly, the now more abundant Omicron BA.5 lacks this loss-of-function polymorphism in ORF6. Altogether, our findings not only further highlight the key role of ORF6 in the antagonism of the antiviral innate immune response, but also emphasize the importance of studying the role of non-spike mutations to better understand the mechanisms governing differential pathogenicity and immune evasion strategies of SARS-CoV-2 and its evolving variants. ONE SENTENCE SUMMARYSARS-CoV-2 ORF6 subverts bidirectional nucleo-cytoplasmic trafficking to inhibit host gene expression and contribute to viral pathogenesis.

microbiology↗

bioRxiv2021

CUB domain containing protein 1 (CDPC1) is a target for radioligand therapy in castration resistant prostate cancer

PurposeRadioligand therapy (RLT) is relatively unexplored in metastatic castration resistant prostate cancer (mCRPC), with much of the focus having been on bone seeking radionuclides and PSMA-directed RLT. Herein, we evaluated if CUB domain containing protein 1 (CDCP1) can be exploited to treat mCRPC with RLT, particularly for subsets like small cell neuroendocrine prostate cancer (SCNC) that would not be expected to respond to current options. Experimental DesignCDCP1 mRNA levels were evaluated in the RNA-seq data from 119 recent mCRPC biopsies. Protein expression was assessed in twelve SCNC and adenocarcinoma patient derived xenografts. Saturation binding assays were performed with 4A06, a recombinant human antibody that targets the CDCP1 ectodomain. The feasibility of imaging and treating mCRPC in vivo was tested with 89Zr-4A06 and 177Lu-4A06. ResultsCDCP1 mRNA expression was observed in over 90% of mCRPC biopsies, including SCNC and in adenocarcinoma with low FOLH1 (PSMA) levels. A modest anticorrelation was observed between CDCP1 and PTEN. Overall survival was not significantly different based on CDCP1 mRNA levels, regardless of PTEN status. Full length and/or cleaved CDCP1 was expressed in ten of twelve PDX samples. Bmax values of ~22,000 and ~6,200 fmol/mg were calculated for two human prostate cancer cell lines. Five prostate cancer models were readily detected in vivo with 89Zr-4A06. 177Lu-4A06 significantly suppressed the growth of DU145 tumors compared to control. ConclusionsThe antitumor data and the overexpression of CDCP1 reported herein provide the first evidence promoting CDCP1 directed RLT as a treatment strategy for mCRPC. Statement of Translational RelevanceNew targets for RLT are needed to address the subset of mCRPC that cannot be treated with bone seeking radionuclides or PSMA directed RLT. We report herein the first data credentialing CDCP1 as a target for mCRPC, in both adenocarcinoma and neuroendocrine subtypes. Combined with low expression in normal human tissues, these data provide a compelling scientific rationale for testing CDCP1 directed RLT clinically in mCRPC patients alone or in combination with other systemic therapies.

cancer biology↗

bioRxiv2021

Targeting a proteolytic neo-epitope of CUB-domain containing protein 1 in RAS-driven cancer

A central challenge for any therapeutic is targeting diseased over normal cells. Proteolysis is frequently upregulated in disease and can generate proteoforms with unique neo-epitopes. We hypothesize that targeting proteolytic neo-epitopes can enable more effective and safer treatments, reflecting a conditional layer of disease-specific regulation. Here, we characterized the precise proteolytic isoforms of CUB domain containing protein 1 (CDCP1), a protein overexpressed and specifically cleaved in RAS-driven cancers. We validated that the N-terminal and C-terminal fragments of CDCP1 remain associated after proteolysis in vitro and on the surface of pancreatic cancer cells. Using a differential phage display strategy, we generated exquisitely selective recombinant antibodies that target cells harboring cleaved CDCP1 and not the full-length form using antibody-drug conjugates or a bi-specific T-cell engagers. We show tumor-specific localization and anti-tumor activity in a syngeneic pancreatic tumor model having superior safety profiles compared to a pan-CDCP1-targeting antibody. Our studies show proteolytic neo-epitopes can provide an orthogonal "AND" gate for disease-specific targeting. One-Sentence SummaryAntibody-based targeting of neo-epitopes generated by disease-associated proteolysis improves the therapeutic index

biochemistry↗

bioRxiv2020

Mountaintop Removal Mining Threatens the Survival and Recovery of Imperiled Species

Environmental laws need sound data to protect species and ecosystems. In 1996, a proliferation of mountaintop removal coal mines in a region home to over 50 federally protected species was approved under the Endangered Species Act. Although this type of mining can degrade terrestrial and aquatic habitats, the available data and tools limited the ability to analyze spatially extensive, aggregate effects of such a program. We used two large, public datasets to quantify the relationship between mountaintop removal coal mining and water quality measures important to the survival of imperiled species at a landscape scale across Kentucky, Tennessee, Virginia, and West Virginia. We combined an annual map of the extent of surface mines in this region from 1985 to 2015 generated from Landsat satellite imagery with public water quality data collected over the same time period from 4,260 monitoring stations within the same area. The water quality data show that chronic and acute thresholds for levels of aluminum, arsenic, cadmium, conductivity, copper, lead, manganese, mercury, pH, selenium, and zinc safe for aquatic life were exceeded thousands of times between 1985 and 2015 in streams that are important to the survival and recovery of species on the Endangered Species List. Linear mixed models showed that levels of manganese, sulfate, sulfur, total dissolved solids, total suspended solids, and zinc increased by 6.73E+01 to 6.87E+05 {micro}g/L and conductivity by 3.30E+06 {micro}S /cm for one percent increase in the mined proportion of the area draining into a monitoring station. The proportion of a drainage area that was mined also increased the likelihood that chronic thresholds for copper, lead, and zinc required to sustain aquatic life were exceeded. Finally, the proportion of a watershed that was mined was positively related to the likelihood that a waterway would be designated as impaired under the Clean Water Act. Together these results demonstrate that the extent of mountaintop removal mining, which can be derived from public satellite data, is predictive of water quality measures important to imperiled species - effects that must be considered under environmental law. These findings and the public data used in our analyses are pertinent to ongoing re-evaluations of the effects of current mine permitting regulations to the recovery and survival of federally protected species.

ecology↗

bioRxiv2020

Unpacking the eagle collision risk model: practical guidance for wind energy

Climate change is one of the greatest threats facing biodiversity, and solutions to reduce carbon emissions are needed to conserve species. Renewable energies are a prominent means to achieve this goal, but the potential for direct harm to wildlife has raised concerns as these technologies proliferate. To protect biodiversity, approaches that facilitate renewable energy development while protecting species are needed. In the United States wind energy developers must obtain a permit for any Bald or Golden eagles that might be killed at a facility. The U.S. Fish & Wildlife Service estimates fatalities using a Bayesian modeling framework, which combines pre-construction eagle surveys with prior information. The ways in which prior information is incorporated and how pre-construction monitoring affects model outcomes can be unclear to regulated entities and other stakeholders, creating uncertainty in the permitting process and retarding both the build-out of renewable energy and conservation measures for eagles. We conducted a simulation study quantifying the differences in predicted eagle fatalities obtained by incorporating prior information and using only site-specific survey data across a range of scenarios, evaluating the impact of survey effort on the magnitude of this effect. We identified predictable relationships between survey effort, eagle activity, facility size and discrepancies between estimates. We also translated these patterns into real-world financial costs, illustrating the interaction between pre-construction surveys, fatality estimates, and compensatory mitigation obligations in determining permit timing and expense.

ecology↗

bioRxiv2020

Exploiting KRAS-driven Ferroaddiction in Cancer Through Ferrous Iron-Activatable Drug Conjugates (FeADC)

KRAS mutations cause a quarter of cancer mortality and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at dosages required to adequately extinguish RAS/RAF/MAPK signaling. We found that oncogenic KRAS signaling induces ferrous iron (Fe2+) accumulation early in and throughout KRAS-mediated transformation. We used an FDA-approved MEK inhibitor to produce a prototypical Ferrous Iron-Activatable Drug Conjugate (FeADC) which achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor bearing animals, with tumor-selective drug activation producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation and FeADCs hold promise for improving treatment of KRAS-driven solid tumors.

cancer biology↗

bioRxiv2020

Recovery units under the Endangered Species Act could be used more widely

Recovering species is one of the main goals of the Endangered Species Act (ESA). In the face of limited budgets, diverse tools are needed to find efficient solutions. Recovery units may be one such tool - designated portions of a species range that must be recovered individually before an entire species can be considered recovered. Recovery units allow for spatial flexibility in recovery goals and may be used in regulatory decisions such as section 7 consultation. Despite their availability, there is very little information on how recovery units have been developed and used. We mined available public data to determine the number and types of species for which recovery units have been designated; evaluated species and geographic characteristics associated with recovery unit designation; and examined how recovery units have been used in the implementation of the ESA, such as during consultation. We found 49 listed species have designated recovery units through 2017, and that these species had similar characteristics. Namely, they had relatively large ranges and were well-studied. We found taxonomic biases in recovery unit designation as well, with fish species being disproportionately likely to have recovery units and plants disproportionately less. Improvements in recovery priority numbers among species with recovery units indicate that the theoretical benefits of this tool may have translated to improved status. These data indicate that recovery units could be applied to more wide-ranging species to improve recovery under the ESA.

ecology↗

bioRxiv2019

Deep mutational scanning comprehensively maps how Zika envelope protein mutations affect viral growth and antibody escape

Functional constraints on viral proteins are often assessed by examining sequence conservation among natural strains, but this approach is relatively ineffective for Zika virus because all known sequences are highly similar. Here we take an alternative approach to map functional constraints on Zika viruss envelope (E) protein by using deep mutational scanning to measure how all amino-acid mutations to the protein affect viral growth in cell culture. The resulting sequence-function map is consistent with existing knowledge about E protein structure and function, but also provides insight into mutation-level constraints in many regions of the protein that have not been well characterized in prior functional work. In addition, we extend our approach to completely map how mutations affect viral neutralization by two monoclonal antibodies, thereby precisely defining their functional epitopes. Overall, our study provides a valuable resource for understanding the effects of mutations to this important viral protein, and also offers a roadmap for future work to map functional and antigenic selection to Zika virus at high resolution.\n\nImportanceZika virus has recently been shown to be associated with severe birth defects. The viruss E protein mediates its ability to infect cells, and is also the primary target of the antibodies that are elicited by natural infection and vaccines that are being developed against the virus. Therefore, determining the effects of mutations to this protein is important for understanding its function, its susceptibility to vaccine-mediated immunity, and its potential for future evolution. We completely mapped how amino-acid mutations to E protein affected the viruss ability to grow in cells in the lab and escape from several antibodies. The resulting maps relate changes in the E proteins sequence to changes in viral function, and therefore provide a valuable complement to existing maps of the physical structure of the protein.

microbiology↗

bioRxiv2019

Automated Habitat Change Detection Methods using Satellite Data to Improve Conservation Law Implementation

A significant limitation in biodiversity conservation has been the effective implementation of laws and regulations that protect species habitats from degradation. Flexible, efficient, and effective monitoring and enforcement methods are needed to help conservation policies realize their full benefit. As remote sensing data become more numerous and accessible, they can be used to identify and quantify land cover changes and habitat loss. However, these data remain underused for systematic conservation monitoring in part because of a lack of simple tools. We adapted and developed two generalized methods that automatically detect land cover changes in a variety of habitat types using free and publicly available data and tools. We evaluated the performance of these algorithms in two ways. First, we tested the algorithms over 100 sites of known change in the United States, finding these approaches were effective (AUC > 0.90) at distinguishing between areas of land cover change and areas of no change. Second, we evaluated algorithm effectiveness by comparing results to manually identified areas of change in four case studies involving imperiled species habitat: oil and gas development in the range of the Greater Sage Grouse; sand mining operations in the range of the dunes sagebrush lizard; loss of Piping Plover coastal habitat in the wake of hurricane Michael (2018); and residential development in beach mouse habitat. The relative performance of each algorithm differed in each habitat type, but both provided effective means of detecting and delineating habitat loss. Our results show how these algorithms can be used to help close the implementation gap of monitoring and enforcement in biodiversity conservation and we provide a free online tool that can be used to run these analyses. Article impact statementMethods for automating the detection of habitat loss in satellite images that can be used to monitor and enforce conservation policy.

ecology↗

bioRxiv2019

30 years of satellite data show imperiled species are most vulnerable to habitat loss on private lands

To stem the ongoing loss of biodiversity, there is an urgent need to distinguish between effective and ineffective approaches for protecting species habitats. Using Google Earth Engine and 30 years of Landsat images, we quantify habitat change for 24 vertebrates on the U.S. Endangered Species List (ESA) and IUCN Red List across different categories of land ownership (e.g., federal, state, and private) that are subject to different conservation-focused legal restrictions. These estimates exclude changes due to agricultural conversion and burned areas. Imperiled species evaluated lost the least habitat (3.6%) on federal lands, while losses on private lands without conservation easements were more than twice as great (8.1%). Differences in annual percent loss before and after species were placed on the Endangered Species List, and between ESA and Red List species suggest that the ESA limited habitat loss and was most effective on federal lands. These results emphasize the importance of federal lands for protecting habitat for imperiled species and highlight the need to improve habitat protection on private lands for long-term conservation.

ecology↗

bioRxiv2018

Zika Virus Subverts Stress Granules to Promote and Restrict Viral Gene Expression

Flaviviruses limit the cell stress response by preventing the formation of stress granules and utilize different proteins involved in the stress granule pathway to modulate viral gene expression. In this study, we investigated the formation of stress granules during Zika virus (ZIKV) infection and the role stress granule proteins play during the viral life cycle. Using immunofluorescence and confocal microscopy, we determined that ZIKV disrupted the formation of arsenite-induced stress granules and changed the subcellular distribution, but not the abundance or integrity of stress granule proteins. To investigate the role of different stress granule proteins in ZIKV infection we used target-specific siRNAs to deplete six proteins, namely Ataxin2, G3BP1, HuR, TIA-1, TIAR and YB-1. Depletion of TIA-1 and TIAR affected ZIKV protein and RNA levels, but viral titers did not change. Conversely, depletion of Ataxin2 and YB-1 decreased virion production despite having only a small effect on ZIKV protein and expression. Notably, however, depletion of G3BP1 and HuR decreased and increased ZIKV gene expression and virion production, respectively. Using an MR766 Gaussia luciferase reporter genome together with knockdown and overexpression assays, G3BP1 and HuR were found to modulate ZIKV replication. These data indicate that ZIKV disrupts the formation of stress granules by sequestering stress granule proteins required for replication, which is where G3BP1 functions to promote ZIKV infection, while HuR exhibits an antiviral effect. The consequence of ZIKV re-localizing and subverting select stress granule proteins might have broader consequences on cellular RNA homeostasis contributing to cellular gene dysregulation and ZIKV pathogenesis.\n\nImportanceIn response to viral infection, cellular translation is stalled, and translation initiation complexes, cellular mRNAs, and RNA binding proteins aggregate in stress granules. Because the assembly of stress granules antagonize translation of viral proteins, which is a critical step for single-stranded positive-sense RNA viruses to replicate the viral genome, many viruses have developed strategies to inhibit stress granule formation. In this study, we observed that Zika virus restricts the formation of stress granules likely by re-localizing specific stress granule proteins during infection. We also determined that specific stress granule proteins function to facilitate and limit Zika virus replication. This interaction of Zika virus with stress granule proteins is interesting, as many stress granule proteins are also known to function in neuronal granules, which are critical in neural development and function. Moreover, dysregulation of different stress granule proteins in neurons has been shown to play a role in the progression of neurodegenerative diseases. The likely consequences of Zika virus modulating stress granule assembly and subverting specific stress granule proteins are alterations to cellular mRNA transcription, splicing, RNA stability, and translation. Such changes in cellular ribostasis could have profound effects on neural development and contribute to the devastating developmental and neurological anomalies observed following intrauterine Zika virus infection. Our study provides new insights into virus-host interactions and the identification of the stress granule proteins that may contribute to the unusual pathogenesis associated with this reemerging arbovirus.

microbiology↗

bioRxiv2018

Data indicate the importance of expert agencies in conservation policy.

AO_SCPCAPBSTRACTC_SCPCAPData on the implementation of laws and policies are essential to the evaluation and improvement of governance. For conservation laws like the U.S. Endangered Species Act (ESA), such data can inform actions that may determine the persistence or extinction of species. A central but controversial part of the ESA is section 7, which requires federal agencies to conserve threatened and endangered species. One way they do this is by consulting with expert agencies for the ESA, the U.S. Fish and Wildlife Service (FWS) and the National Marine Fisheries Service (NMFS), on actions they may undertake that impact listed species. Using data from all 24,893 consultations recorded by NMFS from 2000 through 2017, we show that federal agencies misestimated the effects of their actions on listed species in 21% of consultations, relative to the conclusions reached by NMFS. In 71% of these cases the federal agency underestimated the effects of their action. Those discrepancies were particularly important for the conservation of 14 species in 22 consultations, where the agency concluded that its action would not harm a species, while NMFS determined the action would jeopardize the species existence. Patterns of misestimation varied among federal agencies, and some of the agencies most frequently involved in consultation also frequently misestimated their effects. Jeopardy conclusions were very rare--about 0.3% of consultations--with a few project types more likely to lead to jeopardy. These data highlight the importance of consultation with the expert agencies and reveal opportunities to make the consultation process more effective.\n\nSO_SCPCAPIGNIFICANCE STATEMENTC_SCPCAPThe US Endangered Species Act is the strongest environmental law any nation has enacted to conserve imperiled species. However, policy debates over how the Act should be implemented continue to this day. This study provides the first comprehensive evaluation of how the National Marine Fisheries Service (NMFS) implements one of the Acts most important conservation programs - consultations under section 7. Our results reveal novel insights into the importance of NMFS role in ensuring federal actions do not jeopardize the existence of listed species. By using data to inform policy debate, we identify approaches to implementing section 7 that would undermine the conservation of imperiled species, and those that could improve the efficiency of the program without sacrificing these protections.

ecology↗