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ABSTRACT Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Introduction Increasingly in pharmacoepidemiology, linking is required to enrich analytic data to more accurately define study populations, enable adjustment for confounding, and improve capture of health outcomes. When creating such novel linked datasets, researchers should consider their suitability to meet research objectives, assess source data completeness and population coverage, and ensure well-defined data governance standards and protections exist. Additionally, while the RECORD-PE guidelines assist in the reporting of studies using observational health data specific to pharmacoepidemiology, they do not address the unique requirements for transparent evaluation and reporting of the data linkage process. Objectives and Approach We aimed to 1) provide guidance on data linkage appropriateness and feasibility to plan purposeful and sustainable new linkages that advance pharmacoepidemiological research and 2) generate a checklist with specific recommendations to assist researchers in providing clear and transparent assessment of the linkage process. To develop these guidelines, a working group comprised of members of the International Society of harmacoepidemiology was formed. Recommendations were open for comment by Society members and endorsed by the Society. Results Guidance for feasibility assessment was categorized into five domains: (1) research objectives and justification; (2) data quality and completeness; (3) the linkage process; (4) data ownership and governance; and (5) overall value added by linkage. A checklist for evaluation and reporting of data-linkage processes covered five domains including; (1) data sources; (2) linkage variables; (3) linkage methods; (4) linkage results; and (5) linkage evaluation, including validation and verification of the resulting linked data. Conclusion/Implications Our guidelines for data linkage feasibility assessment and reporting can be used to inform the design of sustainable linked data resources and for transparent communication of linkage processes. Together, these guidelines will help various stakeholders to critically assess the potential for bias in research based on linked data and help generate actionable evidence.

West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease.

A two-year study was conducted in Maine wild blueberry fields (Vaccinium angustifolium Aiton) on the health of migratory honey bee colonies in 2014 and 2015. In each year, three or five colonies were monitored at each of nine wild blueberry field locations during bloom (mid-May until mid-June). Colony health was measured by assessing colony strength during wild blueberry bloom. Potential factors that might affect colony health were queen failure or supersedure; pesticide residues on trapped pollen, wax comb, and bee bread; and parasites and pathogens. We found that Varroa mite and pesticide residues on trapped pollen were significant predictors of colony health measured as the rate of change in the amount of sealed brood during bloom. These two factors explained 71% of the variance in colony health over the two years. Pesticide exposure was different in each year as were pathogen prevalence and incidence. We detected high prevalence and abundance of two recently discovered pathogens and one recently discovered parasite, the trypanosome Lotmaria passim Schwartz, the Sinai virus, and the phorid fly, Apocephalus borealis Brues.