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Pulendran and colleagues delineated the mechanisms underlying the nonspecific antiviral effects exerted by the BCG vaccine against SARS-CoV-2 and reveal a pivotal role for BCG-specific CD4⁺ T cells that produce interferon-γ in imprinting a persistent antiviral innate program in the lung, mediating heterologous viral protection.

Hepatitis C virus utilizes flavin adenine dinucleotide as a non-canonical initiating nucleotide for the viral RNA polymerase, resulting in 5′ capping of viral RNA, which provides protection against the host innate immune response.

The way in which metastatic tumour cells control endocytic vesicular trafficking networks to establish a front-rear polarity axis that facilitates motility remains unclear. Here, the authors show that the EMT activator ZEB1 influences vesicular trafficking dynamics to execute cell polarity change.

Endoribonuclease PA-X allows influenza A virus to discriminate between viral and host transcripts by cleaving GCUG tetramers.

Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses.

Radiotherapy is known to cause heart disease. A recent analysis challenges several long-held tenets, indicating that radiation-induced cardiotoxicity might occur at lower doses, and earlier, than generally believed. We must be mindful of this toxicity and limit cardiac radiation dose as much as possible.

Here, the authors perform simultaneous inoculation of genetically tagged influenza A virus in ferrets and show that airborne transmissible viruses are preferentially transmitted from the upper respiratory tract, which correlates with high replication ability in the ferret and human nasal respiratory epithelium.

Direct interaction of influenza virus with Gram-positive and Gram-negative bacterial pathogens of the respiratory tract results in increased bacterial adherence to respiratory epithelial cells in culture and in higher bacterial burdens in vivo.

Virus reassortment drives genetic diversity and evolution and is governed by intra-host dynamics that are less well understood. Here, the authors characterise the within-host dynamics of influenza A virus reassortment in swine, ferrets and guinea pigs, considering their spatial distribution.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

The neuraminidase-targeting monoclonal antibody FNI9 potently inhibits the enzymatic activity of influenza A and B viruses via receptor mimicry.

The soluble neurotrophic factor GDNF promotes trans-synaptic adhesion through its co-receptor GFRα1. Here, the authors describe the structural basis for GDNF-GFRα1 adhesion and reconstitute assemblies bridging membranes, demonstrating that binding of either the RET receptor or proteoglycans can disrupt this adhesive function.

Fibrocystin/Polyductin (FPC) is a large ciliary membrane protein encoded by PKHD1 which, when mutated, causes ARPKD. Here, the authors show that FPC suppresses cyst development in the kidney of mouse models through the release and mitochondrial translocation of its C terminal product.

Here, Broszeit et al. show that circulating A/H3N2 viruses have evolved binding specificity to α2,6-sialosides on extended LacNAc moieties and therefore cannot agglutinate erythrocytes. Applying glycan remodeling allows to install functional receptors on erythrocytes and promotes identification of newly circulating variants to facilitate vaccine design.

Viral infection of the respiratory system induces exuberant fibroblast activity, resulting in extensive remodelling of the extracellular matrix and cytokine release, which promote immune cell infiltration of the affected area at the expense of respiratory function.

Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.

While biallelic mutations of the SLC26A4 gene cause non-syndromic hearing loss with enlarged vestibular aqueducts or Pendred syndrome, a considerable number of patients carry mono-allelic mutations. Here the authors identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4.

It is believed that human Influenza HA glycoprotein attaches to alpha2-6 linked sialic acids (SA) on cells, while avian viruses bind to alpha2-3 linked sialic acids, therewith contributing to host tropism. Here, Liu et al. show that mixing low-affinity alpha2-3 SA with low amounts of high-affinity alpha2-6 SA increases binding and entry of human viruses and the converse for avian virus. This shows that receptor recognition is not as strict as currently assumed and provides evidence that heteromultivalent interactions between human/avian HA and SA contributes to host adaptation.

In chickens, influenza A virus relies on host protein ANP32A. Here the authors use CRISPR/Cas9 to generate homozygous gene edited chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction.

Thomas and colleagues examine preinfection baseline parameters of cellular and serologic immunity. Their findings collectively show that peripheral cell composition provides better correlates of immune protection from symptomatic influenza infection than vaccination, demographics or serology alone.

Productive influenza infection can be improved by cooperation and this varies between viral strains and hosts. By quantifying the rates of reassortment and virus production using several methods, including single-cell sequencing, the authors find that isolates of the avian H9N2 influenza subtype are dependent on infections with a second virus, but only in mammalian cells and not in avian cells. These findings are supported by in vivo experiments in guinea pigs and quail. The authors find indications that this type of cooperation between influenza A viruses depends on the RNA polymerase subunit PA.

In this Review, the authors examine advances in uromodulin biology, including the existence of non-polymeric forms of the protein, its versatile functions, crosstalk with the immune system, its potential as a biomarker and its role in kidney disease, as well as considering how uromodulin might be targeted therapeutically.

A nanoparticle influenza vaccine candidate is shown to induce broad cross-reactive antibody responses in animal models.

Viral pathogens frequently target host cell antigen-processing pathways, including MHC-I–TAP peptide transporters, to evade host immunity. Blander and colleagues describe how MHC-I molecules can still cross-present antigen by re-routing ERGIC-resident MHC molecules to phagosomal vesicles, where phagolysosomal proteases act to shape the peptide repertoire for MHC-I presentation.

Geochemical insights from a dataset of carbonate stable strontium isotopes suggest that porewater production of authigenic carbonates may have been an overlooked carbonate sink for much of Earth’s history.

The interferon response has been shown to be linked to severity of SARS-CoV-2 infection and is an essential component of the immune response to COVID-19. Here the authors stratify patients according to COVID-19 severity and asses the interferon response showing defective responses in severe infection and highlight the importance of assay variables and confounding factors that impact the detection of interferon.

Many biological processes involve spatially confined cells. Deforet et al.observe and model the behaviours of spatially constrained cell monolayers, and demonstrate that confinement alone induces morphogenesis-like processes including spontaneous collective oscillations and transition to three-dimensional growth.

Epsilon toxin (Etx) is a potent pore forming toxin (PFT) produced by Clostridium perfringens. Here authors show the cryo-EM structure of the Etx pore assembled on the membrane of susceptible cells and shed light on pore formation and mutant phenotypes.

Dampened activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in bat primary immune cells in response to infection with multiple zoonotic viruses is caused by decreased transcriptional priming, the presence of a unique splice variant and an altered leucine-rich repeat domain of bat NLRP3.

YETI puts individual -omics experiments in the context of public genomics data by creating an integrated dataset-specific functional network, thus allowing more thorough interpretation of the data.

Influenza viruses are believed to transmit through the air as respiratory droplets or aerosols. In the guinea pig model, Asadi et al. show that influenza virus can also be transmitted as aerosolized fomites, which are microscopic dust particles stirred up from a virus-contaminated environment.

Structures of the assembled matrix protein 1 of influenza A virus in intact virus particles and of oligomers of this protein reconstituted in vitro reveal mechanisms of assembly and disassembly of influenza virus.

It is now revealed, using cell cultures and in silico models, that weakening intercellular contacts is a fundamental process essential for switching from extensile to contractile tissue behaviour.

An antiviral and antibacterial cotton textile based on a fundamentally different principle of incorporating copper ions into the cotton structure at the atomic level is fabricated with excellent air/water retainability and superior mechanical stability.

The role of T cells in modulating the course of influenza infection in humans is not clear. Wilkinson et al. now report that, in the absence of strain-specific humoral immunity, preexisting cytotoxic CD4⁺ T cells limit the severity and duration of symptoms in humans challenged with influenza virus and suggest these CD4⁺ T cell responses might be harnessed in vaccine development.

Population demographics affect influenza transmission at large spatial scales. Here, influenza immunity is shown to vary spatially in a way unexplained by differences in demographics, suggesting that there are aspects of locations that drive influenza transmission other than individual and household risk factors.

De novo lumen formation during vertebrate left–right organizer development is required for body axis establishment. Here the authors utilize zebrafish to demonstrate that the position and cleavage of the cytokinetic bridge in dividing left-right organizer cells dictates tissue morphogenesis.

Generating organized kidney tissues from human pluripotent stem cell is a major challenge. Here, Freedman et al. describe a differentiation system forming spheroids and tubular structures, characteristic of these kidney structures, and using CRISPR/Cas9, delete PKD1/2, to model polycystic kidney disease.

The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

Mutations in the gene encoding the helicase senataxin have well established associations with the neurodegenerative disease ALS. Marazzi et al. show that senataxin can also attenuate virus-triggered responses by controlling RNA polymerase activity at genes encoding antiviral molecules.

Pancreatic ductal adenocarcinomas (PDAC) exhibit complex morphologies challenging to capture in organoid models. Here, the authors develop PDAC organoids that can recreate branched structures and, with the use of a minimal mathematical model, shed light to pathways and processes directing the dynamics of self-organization and branching morphogenesis.

Mutations in the haemagglutinin of H5N1 avian influenza viruses confer transmissibility in ferrets. Here, Wilker et al. show that while within host variability is high, transmitted virus diversity is low suggesting a genetic bottleneck acts during transmission, driven by selection on haemagglutinin genes.

Although aqueous nitrate ions can be electrocatalytically reduced to value added or benign products, the impact of the electrochemical potential on key reaction steps remains poorly understood. Here, using explicit and analytical grand-canonical density functional theory, the authors investigate the potential dependence of nitrate adsorption and dissociation on pure metals and Cu-based single-atom alloys, reporting a correlation with changes in the surface normal dipole moment largely due to partial charge transfer during nitrate adsorption and N-O bond cleavage during dissociation.

Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.