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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
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| 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
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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
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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
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| 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
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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
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| 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
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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
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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
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| 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
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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
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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
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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
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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
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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
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| 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
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| 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
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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
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| 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
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| Open AccessAntibiotics in ingested human blood affect the mosquito microbiota and capacity to transmit malaria
The gut microbiota of malaria-transmitting mosquitoes contributes to the insects’ resistance to the parasite. Here, Gendrin et al. show that antibiotics in ingested human blood alter the mosquito gut microbiota and increase the insect’s survival, fecundity and susceptibility to the parasites.
- Mathilde Gendrin
- , Faye H. Rodgers
- & George K. Christophides
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| Open AccessFerrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors
Ferrets constitute a useful model for influenza research because they are susceptible to human-adapted flu viruses. Here, the authors show that ferrets, like humans, lack a functional CMAH enzyme and synthesize a single type of sialic acid (Neu5Ac), resulting in naturally humanized influenza virus receptors.
- Preston S.K. Ng
- , Raphael Böhm
- & Michael P. Jennings
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| Open AccessA nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice
Bats carry viruses that can cause disease in other animals and in humans. Here, Ishii et al.identify new nairoviruses from African bats and show that some of them can produce a severe haemorrhagic disease in laboratory mice that is similar to Crimean–Congo haemorrhagic fever in humans.
- Akihiro Ishii
- , Keisuke Ueno
- & Hirofumi Sawa
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Using geospatial modelling to optimize the rollout of antiretroviral-based pre-exposure HIV interventions in Sub-Saharan Africa
Widespread use of antiretroviral drugs for HIV prevention is under evaluation in Sub-Saharan Africa. Here, Gerberry et al.use geospatial mathematical modelling to compare potential rollout plans and show that the initial resource allocation decisions will be crucial in determining the success of interventions.
- David J. Gerberry
- , Bradley G. Wagner
- & Sally Blower
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| Open AccessContrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis
Several drug combinations with different properties are used for malaria treatment. Here, Okell et al. use a mathematical model to simulate malaria transmission and treatment with two drug combinations in Africa, and find that locally optimized policies can be highly cost effective for reducing malaria burden.
- Lucy C. Okell
- , Matthew Cairns
- & Azra C. Ghani
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| Open AccessExosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity
Mammalian cell-derived exosomes can carry RNA and proteins from cell to cell, but this mode of transport has not been shown in nematodes. Here the authors show that a gastrointestinal parasite secretes exosomes that transfer microRNAs to mammalian cells and regulate innate immunity.
- Amy H. Buck
- , Gillian Coakley
- & Rick M. Maizels
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| Open AccessPyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum
Novel antimalarial drugs are urgently needed to combat parasite drug resistance. Here, Vaidya et al. describe a new chemical class of potent antimalarial compounds that act by disrupting the parasite's sodium homeostasis.
- Akhil B. Vaidya
- , Joanne M. Morrisey
- & Lawrence W. Bergman
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Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis
The fungus Cryptococcus neoformans can cause lethal meningoencephalitis in humans after initiating infection in the lung. Here, the authors describe the roles played by two C. neoformanscopper transporters in pathogen’s survival during lung and brain infection.
- Tian-Shu Sun
- , Xiao Ju
- & Chen Ding
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| Open AccessOmega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo
Schistosomiasis, a neglected tropical disease, is caused by flatworms such as Schistosoma mansoni. Here, Hagen et al. describe a lentivirus-based transduction system to deliver microRNA-adapted small hairpin RNAs into S. mansonito inhibit transcription of selected genes implicated in the disease process.
- Jana Hagen
- , Neil D. Young
- & Bernd H. Kalinna
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| Open AccessChlamydia infection depends on a functional MDM2-p53 axis
Protein p53 plays key roles in cellular stress responses and is frequently deregulated in cancer. Here the authors show that infection with chlamydiae activates the ubiquitin ligase MDM2 in infected cells, leading to proteasomal degradation of p53 and thus promoting apoptosis resistance.
- Erik González
- , Marion Rother
- & Thomas F. Meyer
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| Open AccessRapid detection of single bacteria in unprocessed blood using Integrated Comprehensive Droplet Digital Detection
Early detection of blood stream infections is essential for providing effective treatments. Here the authors present a system integrating DNAzyme sensors, droplet microfluidics and a high-throughput 3D particle counter that can detect specific, single bacterial cells in blood within a few hours.
- Dong-Ku Kang
- , M. Monsur Ali
- & Weian Zhao
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Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster
Pneumococci can cause a variety of bacterial infections including conjunctivitis. Here, Valentino et al.show that most conjunctivitis-causing pneumococci belong to a closely related group of strains that possess a unique set of putative virulence factors.
- Michael D. Valentino
- , Abigail Manson McGuire
- & Michael S. Gilmore
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| Open AccessProgressive contraction of the latent HIV reservoir around a core of less-differentiated CD4+ memory T Cells
HIV can persist in CD4+T cells of patients receiving long-term antiretroviral therapy. Here the authors show the presence of intrinsic dynamics that progressively contract the latent HIV reservoir around a core of less-differentiated CD4 T-cell memory subsets.
- S. Jaafoura
- , M. G. de Goër de Herve
- & Y. Taoufik
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Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2
The role of IL-2 signalling in the transition of T cells from effector to memory cells is not well defined. Here, the authors show that T-cell receptor interactions with cognate antigen elicit IL-2 secretion from effector cells, which rescues cells from apoptosis and upregulates IL-7 receptor expression, supporting CD4 T-cell memory formation.
- K. Kai McKinstry
- , Tara M. Strutt
- & Susan L. Swain
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| Open AccessClearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients
While several human papilloma virus (HPV) vaccines exist, a highly effective vaccine that mediates regression of HPV-induced tumours is lacking. Here the authors show that a therapeutic DNA vaccine-induced HPV-specific polyfunctional CD8 T cell in 7 out of 9 patients who all exhibited complete regression of lesions and viral clearance.
- Tae Jin Kim
- , Hyun-Tak Jin
- & Young Chul Sung
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Structure-guided discovery of potent and dual-acting human parainfluenza virus haemagglutinin–neuraminidase inhibitors
Human parainfluenza viruses (hPIVs) cause common respiratory diseases in children. Here the authors rationally design small molecules targeting the hPIV haemagglutinin–neuraminidase protein, and show that the compounds inhibit viral entry and exit from cultured cells.
- Patrice Guillon
- , Larissa Dirr
- & Mark von Itzstein
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Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin
HSV-1 is known to evade the immune system by retention of interleukin-1β. Here, the authors show that HSV-1-infected keratinocytes circumvent this mechanism by release of interleukin-1α, which recruits leukocytes and prevents viral dissemination.
- Katelynn A. Milora
- , Samantha L. Miller
- & Liselotte E. Jensen
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| Open Access‘Division of labour’ in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak
Outbreak strains of the pathogenic fungus Cryptococcus gattii display an increased ability to form tubular mitochondria. Here, Voelz et al.show that mitochondrial tubularization is induced by host reactive oxygen species within macrophages and facilitates rapid growth of neighbouring fungal cells.
- Kerstin Voelz
- , Simon A. Johnston
- & Robin C. May
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Host–parasite network structure is associated with community-level immunogenetic diversity
Genes of the major histocompatibility complex (MHC) are crucial for immune response, yet it is unclear what shapes their diversity at a community level. Here, the authors show that indirect effects among rodent hosts and their helminth parasites can play a crucial role in shaping host MHC diversity.
- Shai Pilosof
- , Miguel A. Fortuna
- & Jordi Bascompte
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Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts
Avian influenza viruses can mutate and become infectious to humans, sometimes causing high mortality. Here, Fan et al.identify three mutations in viral protein PB2 that affect virulence in mammalian hosts.
- Shufang Fan
- , Masato Hatta
- & Yoshihiro Kawaoka
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The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue
The protozoan parasite Entamoeba histolyticainvades the colon and remodels the extracellular matrix, and the parasite-derived proteinase A5 (CP-A5) is known to be involved. Here, the authors show that CP-A5 activates metalloproteinases in the host, changing colon architecture and aiding tissue invasion.
- Roman Thibeaux
- , Patrick Avé
- & Elisabeth Labruyère
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Pseudomonas aeruginosa eradicates Staphylococcus aureus by manipulating the host immunity
The airways of patients with cystic fibrosis are colonized by S. aureus during childhood and by P. aeruginosa in adulthood. Here, Pernet et al. show that P. aeruginosa induces bronchial cells to produce a bactericidal protein sPLA2-IIA that contributes to the decline of S. aureusin the airways.
- Erwan Pernet
- , Laurent Guillemot
- & Lhousseine Touqui
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Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test
There is an urgent need for rapid point-of-care tools for tuberculosis diagnosis and antibiotic sensitivity analysis. Here, the authors describe a breath test that, within minutes, detects isoniazid-susceptible Mycobacterium tuberculosisin infected animals.
- Seong W. Choi
- , Mamoudou Maiga
- & Graham S. Timmins
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Primate-specific miR-576-3p sets host defense signalling threshold
miRNAs regulate a range of biological processes, including the immune response and viral infection. Here, the authors perform a genome-wide miRNA mimic screen and identify a miRNA induced by IRF3 during viral infection that regulates viral–host interactions.
- Melanie L. Yarbrough
- , Ke Zhang
- & Beatriz M. A. Fontoura
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eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection
Cells under environmental stress, including viral infections, accumulate RNA molecules stalled in pre-initiation complexes known as stress granules (SG). Here the authors show that the viral protein Gag counters anti-viral stress responses by inhibiting SG assembly during HIV-1 infection.
- Fernando Valiente-Echeverría
- , Luca Melnychuk
- & Andrew J. Mouland
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Carbon nanotubes as in vivo bacterial probes
The non-invasive detection and imaging of bacterial infection in living organisms is increasingly important. Here, the authors demonstrate the use of labelled carbon nanotubes as bacterial probes in living hosts, and are able to image deep tissue infections with higher signal amplification than dye imaging.
- Neelkanth M. Bardhan
- , Debadyuti Ghosh
- & Angela M. Belcher
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| Open AccessUnexpected structure for the N-terminal domain of hepatitis C virus envelope glycoprotein E1
Hepatitis C virus (HCV) gains entry into host cells via envelope glycoproteins E1 and E2. Here, El Omari et al.present the crystal structure of the N terminus of the E1 ectodomain of HCV and show that it adopts a different fold than predicted.
- Kamel El Omari
- , Oleg Iourin
- & David I. Stuart
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Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia
Candidaemia is a common cause of bloodstream infection, but the genetic basis of Candidainfection is poorly understood. Here, the authors identify genetic variation at three loci that increase risk of candidaemia, and show that genes at these loci have a role in antifungal host defence.
- Vinod Kumar
- , Shih-Chin Cheng
- & Mihai G. Netea
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| Open AccessEpigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection
Chronic infection with the bacterium Helicobacter pylori is associated with inflammation and increased risk of gastric cancer. Kiga et al. show that methylation and silencing of the microRNA gene miR-210is associated with infection in humans, and promotes proliferation of gastric epithelial cells in culture.
- Kotaro Kiga
- , Hitomi Mimuro
- & Chihiro Sasakawa
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Respiratory transmission of an avian H3N8 influenza virus isolated from a harbour seal
Avian influenza viruses constantly threaten human health as evidenced by the outbreaks of human H7N9 infections. Here, Karlsson et al. show that an avian H3N8 virus isolated from harbour seals has the potential to infect, cause disease and transmit in mammalian models of influenza virus infection.
- Erik A. Karlsson
- , Hon S. Ip
- & Stacey Schultz-Cherry