Pathogenesis

  • Review Article |

    This Review outlines the gene and protein expression strategies used by viruses to expand the efficiency of their coding and regulatory sequences, and the implications of these mechanisms for developing antiviral agents.

    • Jessica Sook Yuin Ho
    • , Zeyu Zhu
    •  & Ivan Marazzi
  • Article |

    Lung samples collected soon after death from COVID-19 are used to provide a single-cell atlas of SARS-CoV-2 infection and the ensuing molecular changes.

    • Johannes C. Melms
    • , Jana Biermann
    •  & Benjamin Izar
  • Article |

    Imaging mass cytometry of the human lung reveals the cellular composition and spatial architecture during COVID-19 and other acute injuries, enabling the characterization of lung pathophysiology from structural, immunological and clinical perspectives.

    • André F. Rendeiro
    • , Hiranmayi Ravichandran
    •  & Robert E. Schwartz
  • Article |

    Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

    • Gary Middleton
    • , Peter Fletcher
    •  & Lucinda Billingham
  • Article |

    Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKCζ and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.

    • Cameron D. Griffiths
    • , Leanne M. Bilawchuk
    •  & David J. Marchant
  • Article |

    Infection with SARS-CoV-2 in rhesus macaques causes a respiratory disease that recapitulates aspects of COVID-19 in humans, establishing this species as an animal model for investigating the pathogenesis of SARS-CoV-2.

    • Vincent J. Munster
    • , Friederike Feldmann
    •  & Emmie de Wit
  • Article |

    Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

    • Linlin Bao
    • , Wei Deng
    •  & Chuan Qin
  • Article |

    Crystal structure of the Plasmodium falciparum hexose transporter PfHT1 reveals the molecular basis of its ability to transport multiple types of sugar as efficiently as the dedicated mammalian glucose and fructose transporters.

    • Abdul Aziz Qureshi
    • , Albert Suades
    •  & David Drew
  • Article |

    Mycobacterium tuberculosis suppresses the production of inflammatory cytokines by host cells through the host-mediated ubiquitination of a mycobacterial protein, enhancing the interaction of a host signalling inhibitor with another signalling molecule.

    • Lin Wang
    • , Juehui Wu
    •  & Baoxue Ge
  • Letter |

    A subnanometre-resolution cryo-electron microscopy structure of the Rh5–CyRPA–Ripr complex of Plasmodium falciparum provides insights into how this ligand interacts with the receptor basigin in erythrocyte hosts.

    • Wilson Wong
    • , Rick Huang
    •  & Alan F. Cowman
  • Letter |

    DNA damage induces translocation of cyclic GMP–AMP synthase to the nucleus, where it suppresses homologous recombination by interfering with the formation of the PARP1–Timeless complex.

    • Haipeng Liu
    • , Haiping Zhang
    •  & Baoxue Ge
  • Article |

    Comparison of multiple lesions from individual pancreases sheds light on how ancestral clones can spread through the ductal system and give rise to precursor lesions, with acquisition of further mutations leading to pancreatic cancer.

    • Alvin P. Makohon-Moore
    • , Karen Matsukuma
    •  & Christine A. Iacobuzio-Donahue
  • Letter |

    The cell adhesion molecule Mxra8 is identified as a receptor for multiple arthritogenic alphaviruses such as chikungunya virus, and anti-Mxra8 monoclonal antibodies are shown to reduce rates of chikungunya virus infection in mice and a range of human cells.

    • Rong Zhang
    • , Arthur S. Kim
    •  & Michael S. Diamond
  • Article
    | Open Access

    Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

    • Susanne N. Gröbner
    • , Barbara C. Worst
    •  & Stefan M. Pfister
  • Letter |

    A report of RNA 5-methylcytosine oxidation by mammalian Tet2, showing that Tet2 promotes infection-induced myelopoiesis in mice via a mechanism involving the repression of Socs3 mRNA, a previously unknown regulatory role of Tet2 at the epitranscriptomic level.

    • Qicong Shen
    • , Qian Zhang
    •  & Xuetao Cao
  • Letter |

    DNA methylation profiling of virus-specific T cells during acute viral infection in mice provides evidence that a fate-permissive subset of effector CD8 T cells dedifferentiates into long-lived memory T cells.

    • Ben Youngblood
    • , J. Scott Hale
    •  & Rafi Ahmed
  • Letter |

    A product of the soluble epoxide hydrolase enzyme, 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP), is implicated in the pathogenesis of diabetic retinopathy; levels of 19,20-DHDP increase in the retinas of mice and humans with diabetes, and inhibition of its production can rescue vascular abnormalities in a mouse model of the disease.

    • Jiong Hu
    • , Sarah Dziumbla
    •  & Ingrid Fleming
  • Letter |

    Infection of male mice with Zika virus caused testicular and epididymal damage, reduction in sex hormone levels, destruction of germ and somatic cells in the testis, loss of mature sperm and reduction in fertility.

    • Jennifer Govero
    • , Prabagaran Esakky
    •  & Michael S. Diamond
  • Letter |

    Genomic duplications in the SOX9 region are associated with human disease phenotypes; a study using human cells and mouse models reveals that the duplications can cause the formation of new higher-order chromatin structures called topologically associated domains (TADs) thereby resulting in changes in gene expression.

    • Martin Franke
    • , Daniel M. Ibrahim
    •  & Stefan Mundlos
  • Letter |

    Modulation of PI3Kγ activity regulates macrophage polarization during inflammation and cancer, whilst combining PI3Kγ inhibition with immune checkpoint inhibitors leads to synergistic tumour-inhibitory effects.

    • Megan M. Kaneda
    • , Karen S. Messer
    •  & Judith A. Varner
  • Article |

    A high-fat diet increases the number of intestinal stem cells in mammals, both in vivo and in intestinal organoids; a pathway that involves PPAR-δ confers organoid-initiating capacity to non-stem cells and induces them to form in vivo tumours after loss of the Apc tumour suppressor.

    • Semir Beyaz
    • , Miyeko D. Mana
    •  & Ömer H. Yilmaz
  • Letter |

    Treatment of children with human cadaver-derived growth hormone (c-hGH) contaminated with prions resulted in transmission of Creutzfeldt–Jakob disease (CJD); unexpectedly, in an autopsy study of eight such iCJD patients, the authors found amyloid-β deposition in the grey matter typical of that seen in Alzheimer's disease and amyloid-β in the blood vessel walls characteristic of cerebral amyloid angiopathy, consistent with iatrogenic transmission of amyloid-β pathology in addition to CJD and suggests that healthy c-hGH-exposed individuals may also be at risk of Alzheimer's disease and cerebral amyloid angiopathy.

    • Zane Jaunmuktane
    • , Simon Mead
    •  & Sebastian Brandner
  • Letter |

    Cryptosporidium is an important cause of diarrhoeal disease in young children but until now it has been difficult to study; here, the parasite is genetically modified, paving the way for in-depth investigation and the development of effective treatments.

    • Sumiti Vinayak
    • , Mattie C. Pawlowic
    •  & Boris Striepen
  • Review Article |

    Extracellular ATP released from cells during inflammatory responses predominantly functions as a signalling molecule through the activation of purinergic P2 receptors and contributes to both beneficial and detrimental inflammatory responses; this review examines P2 receptor signalling via ATP and its effect on the outcome of inflammatory and infectious diseases.

    • Marco Idzko
    • , Davide Ferrari
    •  & Holger K. Eltzschig
  • Letter |

    The airway mucin Muc5b (but not Muc5ac) is required for mucociliary clearance, defence against bacterial infection in the airways and middle ear, and maintenance of immune homeostasis in the lungs; Muc5b deficiency causes accumulation of apoptotic macrophages, impairment of phagocytosis and reduced production of interleukin-23, leading to infection and inflammation.

    • Michelle G. Roy
    • , Alessandra Livraghi-Butrico
    •  & Christopher M. Evans
  • Letter |

    In neonatal mice, susceptibility to infection is due to an enriched subset of arginase-2-expressing CD71+ erythroid cells, which suppresses the systemic activation of immune cells, thereby protecting neonates against aberrant inflammation triggered by colonization with commensal microbes.

    • Shokrollah Elahi
    • , James M. Ertelt
    •  & Sing Sing Way