Featured
-
-
Article
| Open AccessEvaluation of candidate vaccine approaches for MERS-CoV
Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development.
- Lingshu Wang
- , Wei Shi
- & Barney S. Graham
-
Article
| Open AccessPlasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice
Mice engrafted with human cells are useful models for research on human malaria parasites. Here the authors show that the complete life cycle of Plasmodium falciparum and the liver stages of Plasmodium ovalecan be studied in mice doubly engrafted with human primary hepatocytes and red blood cells.
- Valérie Soulard
- , Henriette Bosson-Vanga
- & Dominique Mazier
-
Article
| Open AccessCarbohydrate scaffolds as glycosyltransferase inhibitors with in vivo antibacterial activity
The inhibition of bacterial glycosyltransferase has the potential to be an effective therapeutic target against drug resistance bacteria. Here, the authors present a novel class of inhibitor compounds based on a monosaccharide scaffold, which are able to eliminate bacterial infections in mice.
- Johannes Zuegg
- , Craig Muldoon
- & Matthew A. Cooper
-
Article
| Open AccessAn autoinhibitory mechanism modulates MAVS activity in antiviral innate immune response
The cellular protein RIG-I detects viral RNA and activates another protein, MAVS, which then forms filaments and stimulates an antiviral pathway. Here, the authors identify different regions within MAVS involved in activating transcription factors IRF3 and NF-κB, and in MAVS self-inhibition.
- Yuheng Shi
- , Bofeng Yuan
- & Fajian Hou
-
Article
| Open AccessEpstein–Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma
Epstein–Barr virus is associated with nasopharyngeal carcinoma and previous studies have focused on the role of viral proteins in tumour pathology. Here, the authors show that a viral miRNA targets the host protein PTEN and has a critical role in the late stage of nasopharyngeal carcinoma by driving tumour metastasis.
- Longmei Cai
- , Yanfen Ye
- & Xin Li
-
Article
| Open AccessEarly emergence of Yersinia pestis as a severe respiratory pathogen
Yersinia pestis, which evolved from a gastrointestinal pathogen, causes pneumonic and bubonic plague. Here Zimbler et al. show that the gain of a single protein enabled Y. pestisto first cause pneumonic plague, and one amino-acid change in the same protein then allowed the bacteria to efficiently cause bubonic plague.
- Daniel L. Zimbler
- , Jay A. Schroeder
- & Wyndham W. Lathem
-
Article
| Open AccessCaenorhabditis elegans is a useful model for anthelmintic discovery
Screening for new anthelmintic compounds that are active against parasitic nematodes is costly and labour intensive. Here, the authors use the non-parasitic nematode Caenorhabditis elegansto identify 30 anthelmintic lead compounds in an effective and cost-efficient manner.
- Andrew R. Burns
- , Genna M. Luciani
- & Peter J. Roy
-
Article
| Open AccessLucilia cuprina genome unlocks parasitic fly biology to underpin future interventions
Lucilia cuprina is a parasitic blowfly of major economic importance worldwide that feeds on the tissues of animals such as sheep. Here, the authors sequence the genome of L. cuprinaand provide insights into the fly’s molecular biology, interactions with the host animal and insecticide resistance.
- Clare A. Anstead
- , Pasi K. Korhonen
- & Robin B. Gasser
-
Article
| Open AccessThe immunomodulating V and W proteins of Nipah virus determine disease course
Nipah virus (NiV) can be transmitted from bats and other animals to humans, causing severe encephalitis and respiratory disease. Here, Satterfield et al.show that the W protein of NiV modulates the host immune response and determines disease course in a ferret model of infection.
- Benjamin A. Satterfield
- , Robert W. Cross
- & Chad E. Mire
-
Article
| Open AccessA mosquito lipoxin/lipocalin complex mediates innate immune priming in Anopheles gambiae
A soluble factor induced by Plasmodiuminfection promotes hemocyte differentiation and increases mosquitoe resistance to subsequent infections. Here the authors show that this factor consists of a Lipocalin/Lipoxin A4 complex, and that insects can metabolize arachidonic acid to produce lipoxins.
- Jose Luis Ramirez
- , Giselle de Almeida Oliveira
- & Carolina Barillas-Mury
-
Article
| Open AccessConserved Omp85 lid-lock structure and substrate recognition in FhaC
The fundamental processes of protein insertion and translocation at the outer membrane are mediated by Omp85 proteins. Here the authors report structures of the translocase FhaC, showing that the critical L6 loop adopts a conformation similar to that of related insertases; establishing a common structural basis for Omp85 function.
- Timm Maier
- , Bernard Clantin
- & Vincent Villeret
-
Article
| Open AccessTotal synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity
Phosphatidylinositol mannosides are cell envelope components vital for the survival of M. tuberculosis. Here, the authors report an elegant and convergent total synthesis of the complex glycolipid tetraacylated phosphatidylinositol hexamannoside (Ac2PIM6) and study the immunological effects in mice.
- Pratap S. Patil
- , Ting-Jen Rachel Cheng
- & Shang-Cheng Hung
-
Article
| Open AccessContrasting host–pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes
Microsporidia are intracellular parasitic fungi that infect diverse animal hosts including humans. Here, Desjardins et al.present genomic and transcriptomic data for two microsporidia that infect disease-transmitting mosquitoes, highlighting differences in potential host interplay mechanisms.
- Christopher A. Desjardins
- , Neil D. Sanscrainte
- & Christina A Cuomo
-
Article |
IL-10-producing intestinal macrophages prevent excessive antibacterial innate immunity by limiting IL-23 synthesis
Innate immune responses are regulated in the intestine to prevent excessive inflammation. Here the authors demonstrate a pivotal role for intestinal macrophages that constitutively produce IL-10 in controlling excessive innate immune activation and preventing tissue damage after an acute bacterial infection.
- Petra Krause
- , Venetia Morris
- & Masako Murai
-
Article
| Open AccessFour decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain
The early origin and evolution of multidrug resistant strains of Mycobacterium tuberculosisare poorly understood. Here, the authors perform genomic and phylogenetic analyses of 252 clinical isolates from a tuberculosis outbreak in Argentina and reconstruct the timeline of the acquisition of antibiotic resistance.
- Vegard Eldholm
- , Johana Monteserin
- & Francois Balloux
-
Article
| Open AccessExpression of the vault RNA protects cells from undergoing apoptosis
Cellular functions of the vault complex, a large ribonucleoprotein assembly remain elusive. Here, the authors show that Epstein–Barr virus infection enhances the expression of the vault complex-associated RNAs, which leads to improved survival of infected cells due to the inhibition of cell apoptosis.
- Melanie Amort
- , Birgit Nachbauer
- & Norbert Polacek
-
Article |
ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms
The life cycle of parasitic hookworms includes a developmental stage in the lungs, before reaching the gut where they mature into adults. Here Bouchery et al. show that Group 2 innate lymphoid cells (ILC2s) cooperate with CD4+T cells to inhibit the development of a model hookworm in the lungs of mice.
- Tiffany Bouchery
- , Ryan Kyle
- & Graham Le Gros
-
Article
| Open AccessDeoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria
Fluoroquinolone antibiotics are widely used to treat serious bacterial infections, but resistance is an increasing problem. Here the authors describe the synthesis and characterization of novel deoxynybomycin derivatives that exhibit activity against fluoroquinolone-resistant infections in an in vivomodel.
- Elizabeth I. Parkinson
- , Joseph S. Bair
- & Paul J. Hergenrother
-
Article |
In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa
Tripartite multidrug efflux pumps are important determinants of antibiotic resistance in several pathogenic bacteria. Here Verchère et al. design an in vitro assay system to study the transport properties of the MexAB-OprM efflux pump from Pseudomonas aeruginosa.
- Alice Verchère
- , Manuela Dezi
- & Martin Picard
-
Article
| Open AccessAnalysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization
HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.
- Joseph R. Francica
- , Zizhang Sheng
- & Robert A. Seder
-
Article
| Open AccessReduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes
Diabetes can be caused by viral infections in humans and some inbred mice, suggesting genetic predisposition. Here the authors show that mutations in Tyk2 gene underlie susceptibility to virus-induced diabetes in mice, due to Tyk2requirement for antiviral response in insulin-producing cells.
- Kenichi Izumi
- , Keiichiro Mine
- & Seiho Nagafuchi
-
Article
| Open AccessEighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe
Tuberculosis was once a major killer in Europe. Here the authors use metagenomics to obtain genomic sequences of Mycobacterium tuberculosisfrom human remains from eighteenth-century Hungary, revealing mixed infections within individuals as well as presence of the same strain in two individuals.
- Gemma L. Kay
- , Martin J. Sergeant
- & Mark J. Pallen
-
Article
| Open AccessGenomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis
The bacterium Streptococcus suiscauses respiratory tract infections in pigs and meningitis in humans. Here, the authors show that human disease isolates are limited to a single virulent population and find no consistent genomic differences between pig and human isolates.
- Lucy A. Weinert
- , Roy R. Chaudhuri
- & Vanessa Terra
-
Article
| Open AccessTriaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate
The emergence of resistant Plasmodiumstrains fuels the search for new antimalarials. Here, the authors present a new class of potent antimalarial compounds, the triaminopyrimidines, that display low toxicity and long half-life in animal models.
- Shahul Hameed P.
- , Suresh Solapure
- & Vasan K. Sambandamurthy
-
Article |
A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum
Malaria parasites generate metabolic energy through anaerobic glycolysis, yielding lactate that is then secreted out of the parasite cell by an unknown transporter. Here, Marchetti et al. identify and characterize a transporter that may be carrying out such a function in Plasmodium.
- Rosa V. Marchetti
- , Adele M. Lehane
- & Kiaran Kirk
-
Article |
HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus
Many viruses take advantage of microtubule-dependent motor proteins to move through the cell. Malikov et al. show that HIV-1 recruits the kinesin-1 adaptor FEZ1, and that the opposing activities of kinesin-1 and dynein motors are both required for the transport of HIV-1 capsids towards the nucleus.
- Viacheslav Malikov
- , Eveline Santos da Silva
- & Mojgan H. Naghavi
-
Article
| Open AccessMolecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature
Neutrophil extracellular traps (NETs) released by neutrophils trap pathogens but may also cause tissue damage. Here the authors show that during systemic Staphylococcus aureusinfection NETs anchoring to the vasculature are only partially DNase-sensitive, advocating for better anti-NET therapies.
- Elzbieta Kolaczkowska
- , Craig N. Jenne
- & Paul Kubes
-
Article
| Open AccessMulti-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies
Animal models are important to study organismal immune responses to infection with influenza viruses. Here, Fukuyama et al.report a new generation of fluorescently labelled influenza viruses that facilitate the study of viral infections in animal models at cellular level.
- Satoshi Fukuyama
- , Hiroaki Katsura
- & Yoshihiro Kawaoka
-
Article
| Open AccessTrained immunity in newborn infants of HBV-infected mothers
The ability to fight infections matures after birth and is thus termed ‘trained immunity’. Here the authors show that cord blood cells from hepatitis B virus-infected mothers respond more strongly to bacterial infections, suggesting that viral exposure in uteropromotes trained immunity in newborns.
- Michelle Hong
- , Elena Sandalova
- & Antonio Bertoletti
-
Article
| Open AccessEnterohemorrhagic Escherichia coli senses low biotin status in the large intestine for colonization and infection
Enterohaemorrhagic Escherichia coli(EHEC) is an important foodborne pathogen that colonizes the large intestine. Here, the authors identify a signalling pathway that controls EHEC adherence to host cells in response to variations in biotin levels, ensuring selective colonization of the large intestine.
- Bin Yang
- , Lu Feng
- & Lei Wang
-
Article |
IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes
Autophagy is critical for pathogen clearance by innate immune cells. Here the authors show that IRF8 is activated in response to autophagy-inducing stimuli, promotes autophagic progression by driving transcription of autophagy genes and is critical for clearance of intracellular bacteria.
- Monica Gupta
- , Dong-Mi Shin
- & Keiko Ozato
-
Article
| Open AccessIL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology
Macrophages and dendritic cells contribute to gut homeostasis and mucosal immune defense. Here, Aychek et al. describe an IL-23-based crosstalk between these cells that prevents lethal immunopathology during Citrobacter rodentiuminfection.
- Tegest Aychek
- , Alexander Mildner
- & Steffen Jung
-
Article |
Targeting bacteria via iminoboronate chemistry of amine-presenting lipids
The analysis of cell membrane biology, and in particular the constituent lipid content, can yield important information on cell function. Here, the authors present a method to selectively and covalently label amine-presenting lipids in bacterial cell membranes.
- Anupam Bandyopadhyay
- , Kelly A. McCarthy
- & Jianmin Gao
-
Article |
Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells
The CRISPR/Cas9 system can be used for genome editing. Here, Liao et al. show that the system can be adapted to inhibit HIV expression and replication, excise the integrated HIV genome and provide long-term protection against new infections in human cells, including pluripotent stem cells.
- Hsin-Kai Liao
- , Ying Gu
- & Juan Carlos Izpisua Belmonte
-
Article
| Open AccessChromatin organization at the nuclear pore favours HIV replication
Retroviruses such as HIV integrate into the host genome as an essential step prior to their replication. Here Lelek et al. identify nuclear pore complex proteins that are essential for HIV nuclear import and productive integration, and show that the intranuclear protein Tpr influences integration into transcriptionally active chromatin.
- Mickaël Lelek
- , Nicoletta Casartelli
- & Francesca Di Nunzio
-
Article |
IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection
The role of IL-10 in influenza infection is controversial. Here the authors show that early during infection, IL-10 promotes Th1 immunity by inhibiting viral neuraminidase-mediated release of TGF-β, but later acts as an immunosuppressive cytokine to inhibit immunopathology and promote recovery.
- Avijit Dutta
- , Ching-Tai Huang
- & Yueh-Chia He
-
Article
| Open AccessCEACAM1 induces B-cell survival and is essential for protective antiviral antibody production
Antibody responses are regulated by selective survival of B cells with proper antigen specificity. Here the authors show that CEACAM1 is critical for B-cell survival during homeostasis and antiviral responses.
- Vishal Khairnar
- , Vikas Duhan
- & Karl S. Lang
-
Article |
Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env
Broadly neutralizing antibodies targeting the Env protein of HIV-1 are being used to guide vaccine design. Here, Guttman et al.show that highly potent antibodies bind to the ‘closed’, prefusion form of Env, whereas less potent antibodies bind only to the ‘open’ form (typical of receptor-bound virus).
- Miklos Guttman
- , Albert Cupo
- & Kelly K. Lee
-
Article |
Mitochondrial Ca2+-dependent NLRP3 activation exacerbates the Pseudomonas aeruginosa-driven inflammatory response in cystic fibrosis
Airway epithelia from cystic fibrosis patients show an exaggerated inflammatory response to P. aeruginosa. Here, Rimessi et al. show that P. aeruginosa exposure causes augmented Ca2+signalling in the absence of functional CFTR, leading to mitochondrial damage and activation of the NLRP3 inflammasome.
- Alessandro Rimessi
- , Valentino Bezzerri
- & Paolo Pinton
-
Article
| Open AccessGenetic blueprint of the zoonotic pathogen Toxocara canis
Toxocara canis is a zoonotic parasite of major worldwide socioeconomic importance. Here, the authors sequence the genome and transcriptome of T. canis, and highlight potential mechanisms involved in development and host–parasite interactions that could support the pursuit of new drug interventions.
- Xing-Quan Zhu
- , Pasi K. Korhonen
- & Robin B. Gasser
-
Article |
Sorting of small infectious virus particles by flow virometry reveals distinct infectivity profiles
Individual viral particles can display heterogeneity in their composition of lipids, proteins or nucleic acids. Here, the authors apply advanced flow cytometry techniques to sort Junin virus particles and show that particle size and envelope glycoprotein concentration correlate with infectivity.
- Raphaël Gaudin
- & Natasha S Barteneva
-
Article |
Dietary restriction protects against experimental cerebral malaria via leptin modulation and T-cell mTORC1 suppression
Nutrition can affect the outcome of infectious diseases through its effects on pathogens and/or host immunity. Here, Mejia et al.show that dietary restriction protects from experimental cerebral malaria in mice through its effects on leptin and mTORC1 in T cells.
- Pedro Mejia
- , J. Humberto Treviño-Villarreal
- & James R. Mitchell
-
Article |
Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity
Intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma displaying biliary phenotypes are aggressive cancers. Fujimoto et al. characterize the mutational profile of chronic hepatitis and identify mutations in KRAS and IDHassociated with poor survival.
- Akihiro Fujimoto
- , Mayuko Furuta
- & Hidewaki Nakagawa
-
Article |
MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs
Mycobacterium tuberculosis possesses several toxin–antitoxin systems of the MazEF family. Here, Tiwari et al. show that these systems contribute to stress adaptation, antibiotic tolerance and virulence.
- Prabhakar Tiwari
- , Garima Arora
- & Ramandeep Singh
-
Article |
Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity
Immune activation must be carefully tuned to respond to infection and restrained to prevent tissue damage. Here the authors show that autophagy has a role in the immune response to Candida albicans, activating NFκB in macrophages by sequestering the NFκB inhibitor A20.
- Masashi Kanayama
- , Makoto Inoue
- & Mari L. Shinohara
-
Article
| Open AccessHuman-to-mosquito transmission efficiency increases as malaria is controlled
Understanding the epidemiology of malaria transmission between humans and mosquitoes is crucial for successful disease control. Analysing data from an 18-year malaria control programme, Churcher et al. show that decreased parasite prevalence in humans can be found concurrently with an increase in transmission efficiency.
- Thomas S. Churcher
- , Jean-François Trape
- & Anna Cohuet
-
Article
| Open AccessThe DNA-binding network of Mycobacterium tuberculosi s
Adaptation of Mycobacterium tuberculosis to the host environment is principally mediated through its transcription factors. Here, the authors report the DNA binding and transcriptional profile of ~80% of all predicted M. tuberculosistranscription factors, and find wide-spread dormant DNA binding.
- Kyle J. Minch
- , Tige R. Rustad
- & David R. Sherman
-
Article |
Structural basis for preferential avian receptor binding by the human-infecting H10N8 avian influenza virus
Avian strains of the influenza virus sometimes infect human hosts with severe consequences. Here, Wang et al.report that the H10N8 avian influenza virus, for which two lethal human infections have been reported, possesses restricted affinity towards the human receptor and suggest a structural basis for H10N8’s limited virulence.
- Min Wang
- , Wei Zhang
- & George F. Gao
-
Article
| Open AccessCo-infection alters population dynamics of infectious disease
Co-infection of plants with multiple pathogen strains is predicted to alter disease dynamics. Here, Susi et al.use experimental and natural population data to show that co-infected host plants spread more disease and cause more devastating epidemics than singly infected hosts.
- Hanna Susi
- , Benoit Barrès
- & Anna-Liisa Laine