Cellular dynamics shape recombination frequency in coronaviruses.

Coronavirus genomes have evolutionary histories shaped extensively by recombination. Yet, how often recombination occurs at a cellular level, or the factors that regulate recombination rates, are poorly understood. Utilizing experimental co-infections with pairs of genetically distinct coronaviruses, we found that recombination is both frequent and rare during coinfection.

A pilot randomized clinical trial of γ-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation.

Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans.

The coronavirus recombination pathway.

Recombination is thought to be a mechanism that facilitates cross-species transmission in coronaviruses, thus acting as a driver of coronavirus spillover and emergence. Despite its significance, the mechanism of recombination is poorly understood, limiting our potential to estimate the risk of novel recombinant coronaviruses emerging in the future. As a tool for understanding recombination, here, we outline a framework of the recombination pathway for coronaviruses.

Plasma sterols and vitamin D are correlates and predictors of ozone-induced inflammation in the lung: A pilot study.

Background: Ozone (O3) exposure causes respiratory effects including lung function decrements, increased lung permeability, and airway inflammation. Additionally, baseline metabolic state can predispose individuals to adverse health effects from O3. For this reason, we conducted an exploratory study to examine the effect of O3 exposure on derivatives of cholesterol biosynthesis: sterols, oxysterols, and secosteroid (25-hydroxyvitamin D) not only in the lung, but also in circulation.

Fish oil blunts lung function decrements induced by acute exposure to ozone in young healthy adults: A randomized trial.

Background: Over one-third of the U.S. population is exposed to unsafe levels of ozone (O).

Classification of new morbillivirus and jeilongvirus sequences from bats sampled in Brazil and Malaysia.

As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxovirus sequences sampled primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirid genomes sequenced from the Americas, including two that are the first full-length bat morbillivirus genome sequences published to date. Our findings add to the vast number of viral sequences in public repositories, which have been increasing considerably in recent years due to the rising accessibility of metagenomics.

Coronavirus and Paramyxovirus Shedding by Bats in a Cave and Buildings in Ethiopia.

Bats are important hosts of zoonotic viruses with pandemic potential, including filoviruses, MERS-Coronavirus (CoV), SARS-CoV -1, and likely SARS-CoV-2. Viral infection and transmission among wildlife are dependent on a combination of factors that include host ecology and immunology, life history traits, roosting habitats, biogeography, and external stressors. Between 2016 and 2018, four species of insectivorous bats from a readily accessed roadside cave and buildings in Ethiopia were sampled and tested for viruses using consensus PCR assays for five viral families/genera.

Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes.

Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods. Given the rise in popularity of nicotine-salt-containing pods and disposable e-cigarettes (fourth generation), we set out to better understand the respiratory effects of these newer e-cigarettes and compare their effects to early-generation devices. We collected induced sputum samples from a cohort of nonsmokers, smokers, third-generation e-cigarette users, and fourth-generation e-cigarette users ( = 20-30 per group) and evaluated the cellular and fluid-phase composition for markers of inflammation, host defense, and lung injury.

Cytokine signature clusters as a tool to compare changes associated with tobacco product use in upper and lower airway samples.

Inhalation exposure to cigarette smoke and e-cigarette aerosol is known to alter the respiratory immune system, particularly cytokine signaling. In assessments of health impacts of tobacco product use, cytokines are often measured using a variety of sample types, from serum to airway mucosa. However, it is currently unclear whether and how well cytokine levels from different sample types and the airway locations they represent are correlated, making comparing studies that utilize differing sample types challenging.

Antimicrobial and Anti-Inflammatory Activity of Apple Polyphenol Phloretin on Respiratory Pathogens Associated With Chronic Obstructive Pulmonary Disease.

Bacterial infections contribute to accelerated progression and severity of chronic obstructive pulmonary disease (COPD). Apples have been associated with reduced symptoms of COPD and disease development due to their polyphenolic content. We examined if phloretin, an apple polyphenol, could inhibit bacterial growth and inflammation induced by the main pathogens associated with COPD.

Zoonotic potential of a novel bat morbillivirus.

Bats are significant reservoir hosts for many viruses with zoonotic potential1. SARS-CoV-2, Ebola virus, and Nipah virus are examples of such viruses that have caused deadly epidemics and pandemics when spilled over from bats into human and animal populations2,3. Careful surveillance of viruses in bats is critical for identifying potential zoonotic pathogens.

Sex-dependent acrolein sensitivity in mice is associated with differential lung cell, protein, and transcript changes.

Acrolein is a reactive inhalation hazard. Acrolein's initial interaction, which in itself can be function-altering, is followed by time-dependent cascade of complex cellular and pulmonary responses that dictate the severity of the injury. To investigate the pathophysiological progression of sex-dependent acrolein-induced acute lung injury, C57BL/6J mice were exposed for 30 min to sublethal, but toxic, and lethal acrolein.

Targeted Hybridization Capture of SARS-CoV-2 and Metagenomics Enables Genetic Variant Discovery and Nasal Microbiome Insights.

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic variants that may alter viral fitness highlights the urgency of widespread next-generation sequencing (NGS) surveillance. To profile genetic variants of the entire SARS-CoV-2 genome, we developed and clinically validated a hybridization capture SARS-CoV-2 NGS assay, integrating novel methods for panel design using double-stranded DNA (dsDNA) biotin-labeled probes, and built accompanying software. This test is the first hybrid capture-based NGS assay given Food and Drug Administration (FDA) emergency use authorization for detection of the SARS-CoV-2 virus.

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling.

Phloretin, an Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction.

Scope: Bacterial infection induces mucus overproduction, contributing to acute exacerbations and lung function decline in chronic respiratory diseases. A diet enriched in apples may provide protection from pulmonary disease development and progression. This study examined whether phloretin, an apple polyphenol, inhibits mucus synthesis and secretion induced by the predominant bacteria associated with chronic respiratory diseases.

Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts.

Albumin is an abundant protein in the lung lining fluid that forms an interface between lung epithelial cells and the external environment. In the lung, albumin can be targeted for adduction by inhaled acrolein. Acrolein, an α,β-unsaturated aldehyde, reacts with biomolecules via Michael addition at the β-carbon or Schiff base formation at the carbonyl carbon.

Systemic inflammatory response to inhaled endotoxin does not correlate with airway response.

Background: Endotoxin is a component of particulate matter linked to respiratory disease. Our group has shown that experimental endotoxin inhalation challenge reproducibly triggers neutrophilic inflammation in the airways and in peripheral blood. Sputum induction is currently the only available method for assessing airway neutrophilia but is laborious and time-consuming.

Author Correction: The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses.

In the version of this Article originally published, the bat species for 12 individuals were incorrectly identified in Supplementary Table 1 and 2. After resequencing the MT-CytB and MT-CO1 segments and reviewing the data, the authors have corrected the errors for these 12 animals. In the amended version of the Supplementary Information, Supplementary Tables 1 and 2 have been replaced to include the corrected host species information.

The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses.

Here we describe the complete genome of a new ebolavirus, Bombali virus (BOMV) detected in free-tailed bats in Sierra Leone (little free-tailed (Chaerephon pumilus) and Angolan free-tailed (Mops condylurus)). The bats were found roosting inside houses, indicating the potential for human transmission. We show that the viral glycoprotein can mediate entry into human cells.

Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma.

Background: We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers.

Objective: We sought to determine whether γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma.

Methods: Participants with mild asthma were enrolled in a double-blinded, placebo-controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins, and cytokines.

Global patterns in coronavirus diversity.

Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrom Coronavirus (MERS-CoV) it has become increasingly clear that bats are important reservoirs of CoVs. Despite this, only 6% of all CoV sequences in GenBank are from bats. The remaining 94% largely consist of known pathogens of public health or agricultural significance, indicating that current research effort is heavily biased towards describing known diseases rather than the 'pre-emergent' diversity in bats.