Featured
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Matters Arising
| Open Access
Common orthopaedic trauma may explain 31,000-year-old remains
- Nicholas J. Murphy
- , Joshua S. Davis
- & Zsolt J. Balogh
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Article |
SARS-CoV-2 infection and persistence in the human body and brain at autopsy
A study reports the distribution, replication and persistence of SARS-CoV-2 throughout the human body including in the brain at autopsy from acute infection to more than seven months following symptom onset.
- Sydney R. Stein
- , Sabrina C. Ramelli
- & Daniel S. Chertow
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Article
| Open Access
Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes
A study examining DNA transfer from mitochondria to the nucleus using whole-genome sequences from 66,083 people shows that this is an ongoing dynamic process in normal cells with distinct roles in different types of cancer.
- Wei Wei
- , Katherine R. Schon
- & Patrick F. Chinnery
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Article |
Enteric viruses replicate in salivary glands and infect through saliva
Enteric viruses replicate in salivary glands, can be propagated in salivary gland-derived spheroids and cell lines, and are released into saliva, which is a new transmission route having implications for therapeutics, diagnostics and sanitation measures.
- S. Ghosh
- , M. Kumar
- & N. Altan-Bonnet
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Article
| Open Access
TLR7 gain-of-function genetic variation causes human lupus
The missense TLR7Y264H gain-of-function genetic variation causes systemic lupus erythematosus in humans and mice.
- Grant J. Brown
- , Pablo F. Cañete
- & Carola G. Vinuesa
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Article |
Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells
Single-cell RNA sequencing and imaging of macrophages in human non-small cell lung cancer and in a mouse model of lung adenocarcinoma show that tissue-resident macrophages have a key role in early tumour progression.
- María Casanova-Acebes
- , Erica Dalla
- & Miriam Merad
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Review Article |
Unconventional viral gene expression mechanisms as therapeutic targets
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
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Article |
A molecular single-cell lung atlas of lethal COVID-19
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
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Article |
Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia
Lungs from patients who died from COVID-19 show atypical fused cells, the formation of which is mediated by the SARS-CoV-2 spike protein, and drugs that inhibit TMEM16F can prevent spike-induced syncytia formation.
- Luca Braga
- , Hashim Ali
- & Mauro Giacca
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Article |
The spatial landscape of lung pathology during COVID-19 progression
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
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Article |
The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis
Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.
- Trevor P. Fidler
- , Chenyi Xue
- & Alan R. Tall
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Article |
Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator
The long non-coding RNA locus Maenli controls mouse limb development by regulating En1 activity, and the absence of the homolgous MAENLI locus is associated with severe congenital limb defects in humans.
- Lila Allou
- , Sara Balzano
- & Andrea Superti-Furga
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Article |
Local immune response to food antigens drives meal-induced abdominal pain
In mice, oral tolerance to food antigens can break down after enteric infection, and this leads to food-induced pain resembling irritable bowel syndrome in humans.
- Javier Aguilera-Lizarraga
- , Morgane V. Florens
- & Guy E. Boeckxstaens
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Article |
Pervasive chromosomal instability and karyotype order in tumour evolution
Chromosomal instability enables the continuous selection of somatic copy number alterations, which are established as ordered events that often occur in parallel, throughout tumour evolution and metastasis.
- Thomas B. K. Watkins
- , Emilia L. Lim
- & Charles Swanton
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Article |
The National Lung Matrix Trial of personalized therapy in lung cancer
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
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Article |
IGF1R is an entry receptor for respiratory syncytial virus
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
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Article |
Respiratory disease in rhesus macaques inoculated with SARS-CoV-2
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
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Article |
The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
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
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Article |
The molecular basis for sugar import in malaria parasites
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
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Article |
Host-mediated ubiquitination of a mycobacterial protein suppresses immunity
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
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Article |
A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1
A dominantly inherited human autoinflammatory disease caused by mutations in RIPK1 is identified, and RIPK1 mutations that prevent caspase-8 cleavage sensitize cells to apoptosis, necroptosis and inflammation.
- Panfeng Tao
- , Jinqiao Sun
- & Qing Zhou
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Matters Arising |
Do not discard Staphylococcus aureus WTA as a vaccine antigen
- Rob van Dalen
- , Michèle M. Molendijk
- & Nina M. van Sorge
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Letter |
Cholera toxin promotes pathogen acquisition of host-derived nutrients
Cholera toxin selectively promotes the growth of Vibrio cholerae through the acquisition of nutrients, including haem and fatty acids, from the host gut.
- Fabian Rivera-Chávez
- & John J. Mekalanos
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Letter |
FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes
Mutations in the transcription factor FOXA1 that are common in prostate cancer result in gain-of-function effects that promote changes in the differentiation of tumour cells.
- Elizabeth J. Adams
- , Wouter R. Karthaus
- & Charles L. Sawyers
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Letter |
Distinct fibroblast subsets drive inflammation and damage in arthritis
Distinct subsets of fibroblasts, which differ in their expression of thymus cell antigen 1 (THY1), are responsible for inflammation and tissue damage in mouse models of arthritis.
- Adam P. Croft
- , Joana Campos
- & Christopher D. Buckley
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Letter |
Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
Histone H4 is released from neutrophil extracellular traps and induces membrane lysis in vascular smooth muscle cells, leading to the destabilization of atherosclerotic plaques.
- Carlos Silvestre-Roig
- , Quinte Braster
- & Oliver Soehnlein
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Letter |
Structure of Plasmodium falciparum Rh5–CyRPA–Ripr invasion complex
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
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Letter |
Nuclear cGAS suppresses DNA repair and promotes tumorigenesis
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
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Brief Communications Arising |
Conflicting evidence for HIV enrichment in CD32+ CD4 T cells
- Liliana Pérez
- , Jodi Anderson
- & Eli A. Boritz
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Article |
Precancerous neoplastic cells can move through the pancreatic ductal system
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
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Letter |
Mxra8 is a receptor for multiple arthritogenic alphaviruses
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
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Article |
Structural basis for dual-mode inhibition of the ABC transporter MsbA
Crystal structures of the ABC transporter MsbA in complex with two selective small-molecule antagonists reveal an unprecedented allosteric mechanism of inhibition.
- Hoangdung Ho
- , Anh Miu
- & Christopher M. Koth
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Article
| Open Access
The landscape of genomic alterations across childhood cancers
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
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Letter |
Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas
In mouse pancreas cells with only one copy of the Nr5a2 gene, the orphan nuclear receptor NR5A2 undergoes a marked transcriptional shift from differentiation-specific to inflammatory genes, which results in an epithelial-cell-autonomous basal pre-inflammatory state.
- Isidoro Cobo
- , Paola Martinelli
- & Francisco X. Real
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Letter |
Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation
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
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Letter |
Effector CD8 T cells dedifferentiate into long-lived memory cells
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
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Letter |
Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy
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
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Letter |
The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition
Combined studies in MYC-driven mouse lymphomas and human Burkitt lymphoma unravel an essential role for the B-cell antigen receptor in the control of tumour B-cell fitness both in vitro and in vivo, with possible biological and clinical implications.
- Gabriele Varano
- , Simon Raffel
- & Stefano Casola
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Letter |
Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes
A mutation that increases the secretion of Zika virus non-structural protein 1 (NS1) in infected hosts enhances the ability of the virus to infect its mosquito vector Aedes aegypti and might have contributed to the recent Zika epidemic.
- Yang Liu
- , Jianying Liu
- & Gong Cheng
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Letter |
Zika virus infection damages the testes in mice
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
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Letter |
Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment
Mutations in the protein tyrosine phosphatase SHP2 affect cells in the bone marrow environment, which leads to aberrant activation of resident haematopoietic stem cells and thereby contributes to the development of leukaemia.
- Lei Dong
- , Wen-Mei Yu
- & Cheng-Kui Qu
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Letter |
Formation of new chromatin domains determines pathogenicity of genomic duplications
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
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Article |
Frizzled proteins are colonic epithelial receptors for C. difficile toxin B
Here, a genome-wide CRISPR–Cas9 screen is used to identify the Wnt receptors frizzled as physiologically relevant Clostridium difficile toxin B receptors, providing new therapeutic targets for treating C. difficile infections.
- Liang Tao
- , Jie Zhang
- & Min Dong
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Letter |
PI3Kγ is a molecular switch that controls immune suppression
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
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Article |
Tumour hypoxia causes DNA hypermethylation by reducing TET activity
- Bernard Thienpont
- , Jessica Steinbacher
- & Diether Lambrechts
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Letter |
A CRISPR screen defines a signal peptide processing pathway required by flaviviruses
Components of the endoplasmic-reticulum-associated signal peptidase complex is required for infection by numerous flaviviruses, including West Nile, dengue and Zika viruses, but is not required for infection by other types of virus or for host protein synthesis.
- Rong Zhang
- , Jonathan J. Miner
- & Michael S. Diamond
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Letter |
Environmental Breviatea harbour mutualistic Arcobacter epibionts
The cultivation of Lenisia limosa, a newly discovered breviate protist, symbiotically colonized by relatives of the animal-associated bacterium Arcobacter.
- Emmo Hamann
- , Harald Gruber-Vodicka
- & Marc Strous
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Article |
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
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
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Letter |
Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples
A DNase sequencing method termed scDNase-seq detects DNase I hypersensitive sites genome-wide in single cells and pools of cells dissected from cancer biopsies.
- Wenfei Jin
- , Qingsong Tang
- & Keji Zhao
C. difficile intoxicates neurons and pericytes to drive neurogenic inflammation