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Molecular adaptations during viral epidemics.

ABSTRACT: In 1977, the world witnessed both the eradication of smallpox and the beginning of the modern age of genomics. Over the following half-century, 7 epidemic viruses of international concern galvanized virologists across the globe and led to increasingly extensive virus genome sequencing. These sequencing efforts exerted over periods of rapid adaptation of viruses to new hosts, in particular, humans provide insight into the molecular mechanisms underpinning virus evolution. Investment in virus genome sequencing was dramatically increased by the unprecedented support for phylogenomic analyses during the COVID-19 pandemic. In this review, we attempt to piece together comprehensive molecular histories of the adaptation of variola virus, HIV-1 M, SARS, H1N1-SIV, MERS, Ebola, Zika, and SARS-CoV-2 to the human host. Disruption of genes involved in virus-host interaction in animal hosts, recombination including genome segment reassortment, and adaptive mutations leading to amino acid replacements in virus proteins involved in host receptor binding and membrane fusion are identified as the key factors in the evolution of epidemic viruses.

SUBMITTER: Rochman ND

PROVIDER: S-EPMC9346483 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Molecular adaptations during viral epidemics.

Rochman Nash D ND Wolf Yuri I YI Koonin Eugene V EV

EMBO reports 20220718 8

In 1977, the world witnessed both the eradication of smallpox and the beginning of the modern age of genomics. Over the following half-century, 7 epidemic viruses of international concern galvanized virologists across the globe and led to increasingly extensive virus genome sequencing. These sequencing efforts exerted over periods of rapid adaptation of viruses to new hosts, in particular, humans provide insight into the molecular mechanisms underpinning virus evolution. Investment in virus geno ...[more]

PMID: 35848484

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Project description:BackgroundIt is necessary to train a large number of healthcare workers (HCW) within a limited time to ensure adequate human resources during an epidemic. There remains an urgent need for best practices on development and implementation of training programmes.ObjectiveTo explore published literature in relation to training and education for viral epidemics as well as the effect of these interventions to inform training of HCW.Data sourcesSystematic searches in five databases performed between 1 January 2000 and 24 April 2020 for studies reporting on educational interventions in response to major viral epidemics.Study eligibility criteriaAll studies on educational interventions developed, implemented and evaluated in response to major global viral outbreaks from 2000 to 2020.ParticipantsHealthcare workers.InterventionsEducational or training interventions.Study appraisal and synthesis methodsDescriptive information were extracted and synthesised according to content, competency category, educational methodology, educational effects and level of educational outcome. Quality appraisal was performed using a criterion-based checklist.ResultsA total of 15 676 records were identified and 46 studies were included. Most studies were motivated by the Ebola virus outbreak with doctors and nurses as primary learners. Traditional didactic methods were commonly used to teach theoretical knowledge. Simulation-based training was used mainly for training of technical skills, such as donning and doffing of personal protective equipment. Evaluation of the interventions consisted mostly of surveys on learner satisfaction and confidence or tests of knowledge and skills. Only three studies investigated transfer to the clinical setting or effect on patient outcomes.Conclusions and implications of findingsThe included studies describe important educational experiences from past epidemics with a variety of educational content, design and modes of delivery. High-level educational evidence is limited. Evidence-based and standardised training programmes that are easily adapted locally are recommended in preparation for future outbreaks.

Project description:L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. To profile the cell-type-specific responses of striatal spiny projection neurons (SPNs) to striatal dopamine depletion, we conducted TRAP analysis of the two major classes of these neurons: dSPNs that express the dopamine receptor 1a (Drd1a), and iSPNs that express the dopamine receptor 2 (Drd2). To disrupt dopamine innervation to both of these SPN populations that reside in the striatum, we injected the neurotoxin 6-hydroxydopamine (6-OHDA), unilaterally, in the medial forebrain bundle (MFB) in hemizygous Drd1-TRAP and Drd2-TRAP adult (9-14 weeks) male mice (kept on a C57BL/6J genetic background). This lesion procedure causes nigral dopamine cell death within a few days, along with a widespread and near-complete loss of dopaminergic innervation to the entire dorsal striatum on one side of the brain (a hemiparkinsonian model). We first examined the effects of dopamine depletion alone, compared to a mock lesion (ascorbate / saline injected). We then examined the effects of chronic levodopa treatment upon the molecular profiles of dopamine- depleted dSPNs and iSPNs, with two dose regimens. The ‘high-dose’ L-DOPA regimen (3 mg/kg on days 1-3, followed by 6 mg/kg on days 4-9) was expected to induce severe dyskinesia in all MFB-lesioned mice. The low-dose L-DOPA regimen (1 mg/kg on days 1-3, followed by 2 mg/kg on days 4-9) was expected to reverse limb use asymmetry without causing conspicuous dyskinesias. To equalize the effects of stress and handling across all groups, including control groups, all mice were equally handled and thus received saline injections when not receiving levodopa injections. Each treatment group contained 7-10 replicates. TRAP-purified mRNAs from either Drd1a- or Drd2-expressing SPNs were reverse-transcribed, amplified, and used to interrogate Affymetrix 430_2.0 GeneChip microarrays.

Project description:BackgroundThe bacterium Coxiella burnetii has caused unprecedented outbreaks of Q fever in the Netherlands between 2007 and 2010. Since 2007, over 4000 human cases have been reported, with 2354 cases in 2009 alone. Dairy goat farms were identified as most probable sources for emerging clusters of human Q fever cases in their vicinity. However, identifying individual farms as primary source for specific clusters of human cases remains a challenge, partly due to limited knowledge of the different C. burnetii strains circulating in livestock, the environment and humans.ResultsWe used a multiplex multi-locus variable number of tandem repeats analysis (MLVA) assay to investigate the genotypic diversity of C. burnetii in different types of samples that were collected nationwide during the Dutch Q fever outbreaks between 2007 and 2010. Typing was performed on C. burnetii positive samples obtained from several independent studies investigating C. burnetii presence in animals and the environment. Six different genotypes were identified on 45 farm locations, based on sequence-confirmed estimates of repeat numbers of six MLVA markers. MLVA genotype A was observed on 38 of the 45 selected farm locations in animals and in environmental samples.ConclusionsSequence confirmation of the numbers of tandem repeats within each locus and consensus about repeat identification is essential for accurate MLVA typing of C. burnetii. MLVA genotype A is the most common genotype in animal samples obtained from goat, sheep, and rats, as well as in environmental samples such as (aerosolized) dust, which is considered to be the major transmission route from animals via the environment to humans. The finding of a single dominant MLVA genotype in patients, the environment, and livestock complicates accurate source-finding. Pinpointing individual sources in the Netherlands requires discrimination of genotypes at a higher resolution than attained by using MLVA, as it is likely that the dominant C. burnetii MLVA type will be detected on several farms and in different patients in a particular area of interest.

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Molecular adaptations during viral epidemics.

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Molecular adaptations during viral epidemics.

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