Pulmonary Cell News Special Issue | Mar 23 2020

Our job is to keep you informed on the top scientific research and news in your field.

In light of COVID-19, we’ve assembled a special issue of Pulmonary Cell News devoted to air-liquid interface (ALI) culture of human primary airway epithelial cells. The ALI culture system has been used to study a wide range of viruses, including the novel coronavirus.

(Ranked by impact factor of the journal)

A Novel Coronavirus from Patients with Pneumonia in China, 2019

Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. [N Engl J Med] Full Article

Genomic Characterization and Epidemiology of 2019 Novel Coronavirus: Implications for Virus Origins and Receptor Binding

Scientists conducted next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. [Lancet] Full Article

A Small-Molecule Fusion Inhibitor of Influenza Virus Is Orally Active in Mice

Benzylpiperazines were identified as a major hit class, with JNJ7918 being the most promising candidate. Consistent with its binding to the functional hemagglutinin stem epitope, this compound also neutralized influenza infection in vitro. [Science] Full Article

Characterization of Orally Efficacious Influenza Drug with High Resistance Barrier in Ferrets and Human Airway Epithelia

To address the unmet need of improved influenza therapy, researchers created EIDD-2801, an isopropylester prodrug of the ribonucleoside analog N4-hydroxycytidine that showed broad anti-influenza virus activity in cultured cells and mice. [Sci Transl Med] Abstract

Viral N⁶-Methyladenosine Upregulates Replication and Pathogenesis of Human Respiratory Syncytial Virus

Investigators showed that RNAs of human respiratory syncytial virus (RSV) were modified by N⁶-methyladenosine within discreet regions and that these modifications enhanced viral replication and pathogenesis. [Nat Commun] Full Article

Influenza A Viruses Are Transmitted via the Air from the Nasal Respiratory Epithelium of Ferrets

Pairs of genetically tagged and untagged influenza A/H1N1, A/H3N2 and A/H5N1 viruses that were transmissible via the air were used to co-infect donor ferrets via the intranasal and intratracheal routes to cause an upper and lower respiratory tract infection. [Nat Commun] Full Article

Modified Cyclodextrins as Broad-Spectrum Antivirals

The authors describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. They showed that the resulting macromolecules were broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses. [Sci Adv] Full Article

Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection

Researchers described overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat coronaviruses (CoVs) using exogenous protease treatment. They found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, mediated infection of Vero and human cells in the presence of exogenous trypsin. [J Virol] Full Article

Species-Specific Colocalization of Middle East Respiratory Syndrome Coronavirus Attachment and Entry Receptors

Investigators established a novel method to detect sialic acids on tissue sections of various organs of different susceptible species by using nanoparticles displaying multivalent Middle East respiratory syndrome coronavirus (MERS-CoV) S1^A. [J Virol] Full Article

Cellular Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Mediates Nuclear Import of Human Bocavirus 1 NP1 Protein and Modulates Viral Capsid Protein Expression

Knockdown of CPSF6 significantly decreased the expression of capsid protein but not that of DEAH-box helicase 15. The authors demonstrated that nuclear protein 1 (NP1) directly interacted with CPSF6 in vitro and colocalized within the virus replication centers. [J Virol] Full Article

Broadly Reactive Anti-Respiratory Syncytial Virus G Antibodies from Exposed Individuals Effectively Inhibit Infection of Primary Airway Epithelial Cells

In order to study the B cell repertoire of three healthy donors for specificity against respiratory syncytial virus (RSV), CD27⁺ memory B cells were isolated and immortalized using BCL6 and Bcl-xL. Of the circulating memory B cells, 0.35% recognized RSV-A2-infected cells. [J Virol] Full Article

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

Applying highly differentiated primary porcine respiratory epithelial cells grown under air-liquid interface conditions, scientists analyzed the contribution of swine influenza viruses to the virulence of S. suis, with a special focus on its cytolytic toxin, suilysin. [J Virol] Full Article

Characterization of Cellular Transcriptomic Signatures Induced by Different Respiratory Viruses in Human Reconstituted Airway Epithelia

Researchers used RNAseq to characterize and compare the transcriptomic signature of infection induced by different major respiratory viruses (influenza viruses, hRSV and hMPV) in a model of reconstituted human airway epithelia. [Sci Rep] Full Article

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Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights from the Upper Airway Epithelium

The authors focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. [Front Cell Dev Biol] Full Article

Advanced In Vitro Lung-on-Chip Platforms for Inhalation Assays: From Prospect to Pipeline

As advanced models capturing the cellular pulmonary make-up at an air-liquid interface, lung-on-chips emulate both morphological features and biological functionality of the airway barrier with the ability to integrate respiratory breathing motions and ensuing tissue strains. [Eur J Pharm Biopharm] Abstract

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