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This study reveals that prion-like domains support the assembly of transcription factor complexes that control fungal cell identity and highlights parallels with the ‘super-enhancers’ that regulate mammalian cell fate.
Subinhibitory levels of sulfamethoxazole, an antibiotic used to treat Escherichia coli infections, trigger a previously undescribed metabolic pathway in E. coli that comprises a family of hybrid pterin–phenylpyruvate conjugates called colipterins. These metabolites are antioxidants, have immunomodulatory properties and improve colitis in a murine model.
Here, the authors identify lymphocyte antigen 6E (LY6E) as a coronavirus (CoV) restriction factor that prevents infection of B cells and dendritic cells. LY6E inhibits both human and mouse CoV entry into cells by interfering with viral spike protein-mediated membrane fusion. It facilitates an antiviral immune response that prevents liver disease and reduces death in the mouse model of MHV-A59 CoV infection.
Metagenomic analysis of a single RNA virome from the Yangshan Deep-Water Harbour in China enabled the recovery of more than 4,500 distinct RNA viruses, doubling the known set of RNA viruses to date, and provided insights into their biology.
Vpu prevents HIV superinfection and immune activation by modulating DNA repair mechanisms, particularly by inhibiting homologous repair. Vpu achieves this by disrupting the RanBP2–RanGAP1*SUMO1–Ubc9 complex at the nuclear pore to reduce PML SUMOylation and consequent PML nuclear body formation, which hampers the homologous recombination factors Rad52 and BLM.
The AcP10 protein—an active uridine kinase, encoded by the beluga whale coronavirus SW1—is an antagonist of the integrated stress response that acts downstream of phosphorylation of the translation initiation factor eIF2, irrespective of which eIF2 kinase is activated. AcP10 acts as a competitive inhibitor of the eIF2[P]–eIF2B interaction by binding to eIF2B. A protein with a similar function is also encoded by Aichivirus, a picornavirus.
The authors propose a nomenclature of SARS-CoV-2 lineages to assist research on epidemiology and decision-making during the COVID-19 pandemic. This nomenclature is based on the SARS-CoV-2 phylogeny and designed to provide a real-time bird’s-eye view of the diversity of the hundreds of thousands of genome sequences collected worldwide. The authors develop a set of rules to produce a hierarchical four-level nomenclature of labels that is flexible and dynamic.
This study highlights a unique drug target for trypanosomatid parasitic protozoa and a new chemical tool for investigating the function of their divergent kinetochores.
In this Article, the authors report the discovery of a small molecule (GHP-88309) that is a new class of allosteric viral polymerase inhibitor that works against two different genera of paramyxoviruses.
Adenovirus produces two early proteins, E1B55K and E4orf6, that become components of the host cell ubiquitin ligase complex comprising elongin-B and C, cullin-5 and RBX1. The authors identified new protein substrates that are ubiquitinated by the E1B55K–E4orf6 complex and find that hnRNP-C and RALY play an inhibitory role on late viral RNA transcripts and that this is counteracted by ubiquitination due to a reduction on the capacity of these proteins to interact with viral RNA.
Bacteria-derived lactate mediates inhibition of HDAC11 during Staphylococcus aureus biofilm infections, resulting in epigenetic changes that reprogramme the host immune response.
This is a comparative analysis of the performance of the primer–probe sets from four open-source molecular diagnostic assays for SARS-CoV-2 recommended by the World Health Organization.
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.
Isolation of phages associated with the gut commensal Bacteroides thetaiotaomicron reveals a link between cell surface structures, including phase-variable capsular polysaccharides, lipoproteins and S-layer proteins, and susceptibility to phage infection.
A microbiome genome-wide association study using three large European cohorts identified several significant study-wide and genome-wide correlations between human genetic variants and microbial traits, and used Mendelian randomization to estimate causal relationships between microbial traits and disease.
This study describes the mechanisms of FOXO1-mediated repression of endoplasmic reticulum (ER) stress in HIV-1 latency. The authors propose a model where inhibition of FOXO1 activity promotes protein accumulation in the ER leading to ER stress signalling and calcium release, which mobilizes ATF4 and NFAT and activates HIV-1 transcription.
Using the proteome-wide pSILAC-AHA labelling approach, the authors resolve the host proteome spatiotemporal dynamics during macrophage infection with Salmonella enterica Typhimurium and reveal the active role of cathepsins in cell death via the non-canonical inflammasome.
In this Article, using a nutrient-limited, media-based compound screening, the authors discover that the old antibiotic rifabutin is highly active against extensively drug-resistant Acinetobacter baumannii.
HIV-1 reverse transcription is found to be completed in the nucleus of the cell using an HIV-1 nuclear import kinetic assay that takes advantage of a nuclear import blockade method to monitor the kinetics of HIV-1 entry and infection.