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| Open AccessMultiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis
Human parechovirus 3 (HPeV3) can cause severe central nervous system infections and is a major cause of neonatal sepsis. Here the authors determine the structure of HPeV3 that provides a high-resolution view of the capsid’s organization and shows multiple interactions of the RNA genome with coat proteins.
- Shabih Shakeel
- , Brenda M. Westerhuis
- & Sarah J. Butcher
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Article
| Open AccessSeptin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV
The accumulation of lipid droplets is often observed in hepatitis C virus infection, but the mechanism of their formation is not known. Here the authors show that septin 9 expression is increased in infected livers, and a septin 9/phosphatidylinositol 5-phosphate signalling pathway regulates the growth of lipid droplets.
- Abdellah Akil
- , Juan Peng
- & Ama Gassama-Diagne
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| Open AccessNeutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins
The role of guanylate-binding proteins (GBPs) in innate immunity is increasingly recognized. Here the authors show that GBP4 activates inflammasome in zebrafish neutrophils, and that this process is critical for the clearance of Salmonellainfection via prostaglandin D2.
- Sylwia D. Tyrkalska
- , Sergio Candel
- & Victoriano Mulero
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Article
| Open AccessA rhesus macaque model of Asian-lineage Zika virus infection
Animal models of infection with Zika virus (ZIKV) are urgently needed for a better understanding of pathogenesis and for testing potential therapies. Here, the authors describe infection of rhesus macaques with an Asian-lineage ZIKV strain as a relevant animal model for studying ZIKV pathogenesis.
- Dawn M. Dudley
- , Matthew T. Aliota
- & David H. O’Connor
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Article
| Open AccessPresenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles
The development of native-like envelope trimers has been a major focus in the efforts to produce HIV vaccines. Here the authors demonstrate the production and characterization of virus-like nanoparticles displaying trimeric HIV-1 antigens with the potential to elicit broadly neutralizing antibodies.
- Linling He
- , Natalia de Val
- & Jiang Zhu
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Article
| Open AccessMAIT cells are activated during human viral infections
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.
- Bonnie van Wilgenburg
- , Iris Scherwitzl
- & Paul Klenerman
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| Open AccessContrasting emergence of Lyme disease across ecosystems
Environmental change is thought to have driven the recent emergence of Lyme disease in Europe. Using a decade of human disease incidence data across a large area in Norway, Mysterud et al.show that incidence correlates with deer population, but that deer population plays a limited role in recent disease emergence.
- Atle Mysterud
- , William Ryan Easterday
- & Hildegunn Viljugrein
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| Open AccessThe innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction
Co-infections with Pseudomonas aeruginosa and Staphylococcus aureus are common in cystic fibrosis patients. Here, the authors show that metal depletion induced by a host protein, calprotectin, promotes co-existence of both pathogens by inhibiting production of anti-staphylococcal molecules by P. aeruginosa.
- Catherine A. Wakeman
- , Jessica L. Moore
- & Eric P. Skaar
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Article
| Open AccessA broad analysis of resistance development in the malaria parasite
It is unclear whether new antimalarial compounds may rapidly lose effectiveness in the field because of parasite resistance. Here, Corey et al.investigate the acquisition of drug resistance and the extent to which common resistance mechanisms decrease susceptibility to a diverse set of 50 antimalarial compounds.
- Victoria C. Corey
- , Amanda K. Lukens
- & Elizabeth A. Winzeler
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| Open AccessLong noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation
Long noncoding RNAs have a wide range of physiological functions, though their role in viral infection and latency is poorly understood. Here the authors show a lncRNA NRON can induce degradation of HIV-1 protein Tat, potentially contributing to latent infection.
- Jun Li
- , Cancan Chen
- & Hui Zhang
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Article
| Open AccessGenome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.
- Yuanfeng Li
- , Lanlan Si
- & Gangqiao Zhou
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Article
| Open AccessThe machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites
Proteins SBP1 and MAHRP1 of the human malaria parasite are required for sequestration of infected red blood cells in major organs. Here, De Niz et al. identify homologous proteins in the rodent parasite Plasmodium berghei, showing that they play similar roles and supporting the usefulness of malaria mouse models.
- Mariana De Niz
- , Ann-Katrin Ullrich
- & Tobias Spielmann
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| Open AccessTRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells
While non-canonical, Atg5/Atg7-independent autophagy has been reported to occur, molecular details of alternative autophagy pathways remain unknown. Here, the authors report that the protein TRIM31 mediates alternative autophagy in intestinal cells, which protects against pathogenic bacteria.
- Eun A. Ra
- , Taeyun A. Lee
- & Boyoun Park
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Article
| Open AccessRelative rate and location of intra-host HIV evolution to evade cellular immunity are predictable
HIV evolves within infected persons to escape being destroyed by the immune system. Here, Barton et al. combine evolutionary dynamics and statistical physics to simulate this process, successfully predicting the relative rate and location of escape mutations in viral sequences for a cohort of HIV-infected persons.
- John P. Barton
- , Nilu Goonetilleke
- & Arup K. Chakraborty
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Article
| Open AccessISG15 deficiency and increased viral resistance in humans but not mice
ISG15 is a ubiquitin-like protein which has important immune-related functions in mice and humans. Here the authors demonstrate that, unlike in mice, human ISG15 stabilizes UPS18 and that ISG15-deficient human cells are more resistant to viral infection.
- Scott D. Speer
- , Zhi Li
- & Dusan Bogunovic
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Article
| Open AccessPseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses
Neutrophil elastase cleaves thrombin generating anti-inflammatory peptides. Here the authors show that cleavage of thrombin by Pseudomonas aeruginosaelastase generates a peptide that prevents TLR dimerization and signaling, interfering with the inflammatory response to avoid host defense.
- Mariena J. A. van der Plas
- , Ravi K. V. Bhongir
- & Artur Schmidtchen
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| Open AccessA human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs
Chikungunya virus is a mosquito transmitted untreatable emergent pathogen that causes joint pain and fever. Here the authors perform a host genome-wide loss-of-function screen to identify targets for chikungunya antiviral drugs and validate hits using a mouse model of chikungunya infection.
- Alexander Karlas
- , Stefano Berre
- & Marc Lecuit
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Article
| Open AccessMost neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits
Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.
- James E. Robinson
- , Kathryn M. Hastie
- & Robert F. Garry
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| Open AccessThe TatD-like DNase of Plasmodium is a virulence factor and a potential malaria vaccine candidate
Neutrophil extracellular traps (NETs), composed of DNA and proteases, contribute to the innate immune response by capturing pathogens. Here, Chang et al. identify a NET-degrading DNase in Plasmodiumparasites and show that immunization with this protein provides protective immunity in a malaria mouse model.
- Zhiguang Chang
- , Ning Jiang
- & Qijun Chen
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| Open AccessAn essential malaria protein defines the architecture of blood-stage and transmission-stage parasites
Blood-stage malaria parasites replicate through a specialised type of cell division known as schizogony. Here, Absalon et al. identify a parasite protein that is essential during schizogony for cytokinesis and formation of the inner membrane complex, the structural scaffold of daughter parasites.
- Sabrina Absalon
- , Jonathan A. Robbins
- & Jeffrey D. Dvorin
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| Open AccessmiRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection
Small RNA plays an important role in regulating the plant defence against bacterial pathogens. Here the authors propose that miR863-3p acts to fine-tune the timing of defence responses by sequentially silencing negative and positive regulators of the plant immune response.
- Dongdong Niu
- , Yifan E. Lii
- & Hailing Jin
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Article
| Open AccessThiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis
When grown in the lab, Mycobacterium tuberculosis can form pellicle biofilms. Here, Trivedi et al. show that thiol reductive stress (induced by dithiothreitol) triggers rapid formation of thicker biofilms containing cellulose as well as antibiotic-tolerant, metabolically active bacteria.
- Abhishek Trivedi
- , Parminder Singh Mavi
- & Ashwani Kumar
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Article
| Open AccessMultivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans
Immunologically-active glycans are promising vaccine candidates but can be difficult to synthesize. Here, the authors show that pentavalent display of a minimal disaccharde epitope on a chemical scaffold can mimic a native C. difficileglycan antigen, representing a simple approach to synthetic vaccine production.
- Felix Broecker
- , Jonas Hanske
- & Peter H. Seeberger
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Article
| Open AccessT-cell activation is an immune correlate of risk in BCG vaccinated infants
BCG vaccine confers only partial protection against tuberculosis. Here the authors show that the risk of tuberculosis infection and progression to disease in BCG-immunized children positively correlates with the frequency of activated HLA-DR+CD4+T cells.
- Helen A. Fletcher
- , Margaret A. Snowden
- & Helen McShane
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Article
| Open AccessDisease dynamics and costly punishment can foster socially imposed monogamy
Many human societies transitioned from polygyny to socially imposed monogamy as group sizes increased. Using a simulation model, the authors show that sexually transmitted infections impose heavier fitness penalties on polygynists as group size grows, enabling monogamists who punish polygyny to thrive in large groups.
- Chris T. Bauch
- & Richard McElreath
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Article
| Open AccessUnconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection
The retromer complex is a multi-protein component of the endosomal protein sorting machinery. Here, Sangaré et al. identify unique features in the retromer complex of the parasite Toxoplasma gondii, and show that it is crucial for the biogenesis of secretory organelles in this pathogen.
- Lamba Omar Sangaré
- , Tchilabalo Dilezitoko Alayi
- & Stanislas Tomavo
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Article
| Open AccessAncient human sialic acid variant restricts an emerging zoonotic malaria parasite
Plasmodium knowlesi infects macaques and can cause malaria in humans. Here, Dankwa et al. show that the absence of a sialic-acid component on the surface of macaque red blood cells (RBCs) limits infection of human RBCs with P. knowlesi, but the parasite can adapt to invade human RBCs by using alternative pathways.
- Selasi Dankwa
- , Caeul Lim
- & Manoj T. Duraisingh
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Article
| Open AccessPrevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance
The fungal pathogen Candida glabrata readily acquires resistance to multiple types of antifungal drugs. Here, Healey et al. show that C. glabrataclinical isolates often carry mutations in a gene involved in DNA mismatch repair, and this is associated with increased propensity to develop antifungal resistance.
- Kelley R. Healey
- , Yanan Zhao
- & David S. Perlin
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| Open AccessGenomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria
African apes harbour six Plasmodium species, one of which gave rise to the human malaria parasite. Here, Sundaraman et al. use selective whole-genome amplification to determine genome sequences from two chimpanzee Plasmodiumspecies, shedding light on the evolutionary origin of the human parasite.
- Sesh A. Sundararaman
- , Lindsey J. Plenderleith
- & Beatrice H. Hahn
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Article
| Open AccessCyclophilin A stabilizes the HIV-1 capsid through a novel non-canonical binding site
The host cell factor cyclophilin A (CypA) interacts with the HIV-1 capsid and regulates infectivity. Here the authors combine cryo-EM, solid-state NMR and all-atom MD simulations, identifying an interaction interface between CypA and the HIV capsid that stabilizes the viral capsid and regulates infectivity.
- Chuang Liu
- , Juan R. Perilla
- & Peijun Zhang
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Article
| Open AccessProtection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules
Neutrophils are critical in preventing the transition of acute peritoneal infection to sepsis. Here the authors show in three mouse models of peritonitis that neutrophils enter the abdominal cavity via high endothelial venules of the greater omentum, and characterize adhesion molecules involved.
- Konrad Buscher
- , Huiyu Wang
- & Jian Song
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Article
| Open AccessSocial amoebae trap and kill bacteria by casting DNA nets
Neutrophils secrete net-like structures made of DNA and anti-microbial peptides, which can trap and kill extracellular pathogens. Here, the authors show that such nets are also produced by so-called Sentinel cells in the multicellular slug stage of the social amoeba Dictyostelium discoideum.
- Xuezhi Zhang
- , Olga Zhuchenko
- & Thierry Soldati
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| Open AccessDynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium
Pneumococci produce a carbohydrate capsule that protects them against components of the host immune system but sensitizes them to host antimicrobial peptides. Here, Kietzman et al.show that pneumococci respond to antimicrobial peptides by capsule shedding, which requires the main autolysin LytA.
- Colin C. Kietzman
- , Geli Gao
- & Elaine I. Tuomanen
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| Open AccessChlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages
Chlamydia trachomatis isolates causing a blinding disease (trachoma) form a single lineage that is different from the lineages causing urogenital infections. Here, Andersson et al. show however that trachoma isolates from Australia are more closely related to urogenital strains than to other trachoma isolates.
- Patiyan Andersson
- , Simon R. Harris
- & Philip M. Giffard
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Article
| Open AccessVector-free transmission and persistence of Japanese encephalitis virus in pigs
Japanese encephalitis virus (JEV) is primarily transmitted between mosquitoes and birds but can also infect pigs. Here the authors demonstrate that JEV, which was thought to be spread exclusively by mosquitoes, can be transmitted between pigs through a direct contact.
- Meret E. Ricklin
- , Obdulio García-Nicolás
- & Artur Summerfield
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Article
| Open AccessGenome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts
Pneumocystis jirovecii is a fungus that can cause life-threatening pneumonia in immunocompromised patients. Here, the authors sequence the genomes of P. jirovecii and two other Pneumocystisspecies, and show the unexpected absence of chitin (a near universal fungal cell wall component).
- Liang Ma
- , Zehua Chen
- & Joseph A. Kovacs
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Article
| Open AccessSelective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
Pathogenic bacteria can aggregate to form biofilms and develop tolerance to antibiotics. Here, the authors use a proteomics approach to study the development of tolerance to the antibiotic colistin in Pseudomonas aeruginosabiofilms, and show that co-treatment with a second compound kills the tolerant cells.
- Song Lin Chua
- , Joey Kuok Hoong Yam
- & Liang Yang
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Article
| Open AccessNeutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
Neutrophils are a major source of IL-1 β in a number of inflammatory settings. Here the authors show that mouse and human neutrophils express functional P2X7 receptors, which mediate ATP-triggered NLRP3 inflammasome activation and IL-1 ß secretion.
- Mausita Karmakar
- , Michael A. Katsnelson
- & Eric Pearlman
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Article
| Open AccessFunctional profiles of orphan membrane transporters in the life cycle of the malaria parasite
The functions of many putative membrane transport proteins of malaria parasites are unknown. Here, Kenthirapalan et al. use mutant strains carrying targeted gene deletions to study the functions of 35 such proteins during the life cycle of Plasmodium bergheiin mosquito and mouse hosts.
- Sanketha Kenthirapalan
- , Andrew P. Waters
- & Taco W. A. Kooij
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Article
| Open AccessA vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium
Iron is an essential nutrient but, in high concentrations, it is also toxic to cells. Here, Slavic et al. identify an iron transporter in malaria parasites that plays a major role in iron detoxification and is required for the parasite’s normal development.
- Ksenija Slavic
- , Sanjeev Krishna
- & Maria M. Mota
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Article
| Open AccessIL-7 signalling represses Bcl-6 and the TFH gene program
It remains incompletely understood how cytokines shape TH1 cell differentiation to central memory T (TCM) and follicular T helper (TFH) cells. Here the authors show that TH1 cells can co-initiate the expression of both TFH and TCM gene programs and that IL-7 signalling represses TFH-associated but not TCM-associated genes.
- Paul W. McDonald
- , Kaitlin A. Read
- & Kenneth J. Oestreich
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| Open AccessPre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination
Ageing is associated with poor responses to vaccines but the underlying mechanism remains unclear. Here the authors use a systems-based approach to define molecular signatures present before vaccination that correlate with non-responsiveness to hepatitis B vaccination in healthy, elderly adults.
- Slim Fourati
- , Razvan Cristescu
- & Rafick-Pierre Sékaly
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Article
| Open AccessStepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
During an immune response, CD4+ T cell repertoire is thought to increase in avidity at the expense of diversity. Here the authors show that B cells act as antigen-presenting cells to boost the development of low-avidity T cell clones, diversifying the T cell repertoire at late stages of the response.
- Julia Merkenschlager
- , Mickaël J. Ploquin
- & George Kassiotis
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Article
| Open AccessInhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA
Coxiella burnetti primarily infects alveolar macrophages and causes an acute form of pneumonia called Q fever. Cunha et al. describe a type IV secretion effector, termed IcaA, expressed by Coxiella burnetiithat inhibits inflammasome activation and therefore may contribute to innate immune evasion by bacteria.
- Larissa D. Cunha
- , Juliana M. Ribeiro
- & Dario S. Zamboni
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Article
| Open AccessRSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection
Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections. Here the authors analyse cellular immune responses of individuals experimentally infected with RSV and reveal the presence of high frequencies of virus- specific resident memory CD8+T cells in the airway, which correlate with improved viral control.
- Agnieszka Jozwik
- , Maximillian S. Habibi
- & Christopher Chiu
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| Open AccessComprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection
Unravelling the mechanism of the recognition of the highly pathogenic influenza A viruses by antibodies is important for understanding their protective function. Zuo et al. characterise the mechanism of recognition of the H5N1 influenza virus by human monoclonal antibodies isolated from convalescent individuals.
- Teng Zuo
- , Jianfeng Sun
- & Linqi Zhang
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Article
| Open AccessRapid emergence and predominance of a broadly recognizing and fast-evolving norovirus GII.17 variant in late 2014
Norovirus GII.4 has been predominating in viral gastroenteritis for 20 years. Here the authors report the emergence and predominance of a novel fast-evolving GII.17 lineage norovirus causing viral gastroenteritis in Hong Kong, with a shift in age distribution of affected individuals towards an older age as compared to GII.4.
- Martin C. W. Chan
- , Nelson Lee
- & Paul K. S. Chan
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| Open AccessSingle-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza A virus infection
Cell-to-cell variability in viral infection means that cell population measurements may not be an accurate representation of the process. Using both experimental and modelling approaches the authors confirm this notion showing that influenza virus infections are variable processes affected by intrinsic and extrinsic noise.
- Frank S. Heldt
- , Sascha Y. Kupke
- & Timo Frensing
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Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3
Epigenetic modulation of hosts by pathogenic bacteria is underexplored. Here, Yaseen et al. show that protein Rv1988 from Mycobacterium tuberculosisenhances microbial survival by methylating histone H3 in the host cell nucleus and thus altering host gene expression.
- Imtiyaz Yaseen
- , Prabhjot Kaur
- & Sanjeev Khosla