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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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Article
| 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
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Pseudomonas aeruginosa adaptation in the nasopharyngeal reservoir leads to migration and persistence in the lungs
Pseudomonas aeruginosa causes chronic infections in patients with lung damage. Here, Fothergill et al. develop an intranasal inhalation model of P. aeruginosainfection and describe genetic and phenotypic changes that the bacteria undergo during adaptation and spread through the respiratory tract.
- Joanne L. Fothergill
- , Daniel R. Neill
- & Aras Kadioglu
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Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin
Mycobacterium tuberculosis acquires iron from its host by producing iron-binding siderophores and by recruiting host transferrin to the phagosome. Here, Boradia et al. show that the bacterial GAPDH protein binds transferrin and drives the uptake of this host protein into M. tuberculosiscells.
- Vishant Mahendra Boradia
- , Himanshu Malhotra
- & Chaaya Iyengar Raje
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Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection
The functional role of microRNAs in the interplay between bacterial pathogens and host cells is not well defined. Here, using an image-based high-throughput screening approach, the authors identify a family of microRNAs that regulates Salmonellainfection and characterize their mechanism of action.
- Claire Maudet
- , Miguel Mano
- & Ana Eulalio
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| Open AccessIdentification of a human neonatal immune-metabolic network associated with bacterial infection
Infection remains a leading cause of morbidity and mortality in neonates worldwide. Here the authors report disproportionate immune stimulatory, co-inhibitory and metabolic pathway responses that specifically mark bacterial infection and can be used to predict sepsis in neonatal patients at the first clinical signs of infection.
- Claire L. Smith
- , Paul Dickinson
- & Peter Ghazal
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Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum
It remains unclear why iron deficiency can protect from malaria infection. Here the authors show that iron-deficient microcytic erythrocytes are less efficiently infected by Plasmodium falciparumparasites and that iron supplementation increases the proportion of young erythrocytes more susceptible to infection.
- Martha A. Clark
- , Morgan M. Goheen
- & Carla Cerami
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An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus
An uncharacterized influenza A-like virus (H17N10) has been detected in bats. Here the authors show that flu viruses containing certain H17N10 genes can infect human cells and mice, but do not exchange genes with other viruses, indicating that H17N10 transmission to humans is not very likely.
- Mindaugas Juozapaitis
- , Étori Aguiar Moreira
- & Martin Schwemmle
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A micro-sterile inflammation array as an adjuvant for influenza vaccines
There is a need of improved adjuvants for influenza vaccines. Here, the authors describe an adjuvant strategy using micro-fractional laser treatment combined with a topical cream containing a TLR 7 ligand that can enhance the immune response to intradermal vaccination with transient, constrained local inflammation.
- Ji Wang
- , Dilip Shah
- & Mei X. Wu
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Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis
Mycobacterium tuberculosisis intrinsically resistant to most antibiotics. Here, the authors show that the pathogen’s tolerance to three antibiotics, each one targeting a distinct cellular process, is mediated by an antioxidant response that requires the activation of isocitrate lyases.
- Madhumitha Nandakumar
- , Carl Nathan
- & Kyu Y. Rhee
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Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells
Ganglioside GM3, a cellular lipid included in the envelope of HIV-1 viral particles, interacts with cellular receptor CD169. Here, the authors develop artificial nanoparticles, consisting of a golden core and a GM3-containing synthetic membrane, that recapitulate the CD169-dependent uptake of viral particles.
- Xinwei Yu
- , Amin Feizpour
- & Björn M. Reinhard
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Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication
Protein modification by small ubiquitin-related modifier (SUMO) proteins is associated with antiviral responses. Here, the authors show that interferons increase the level of expression of SUMO proteins via a let-7 microRNA-controlled mechanism, and this contributes to the antiviral effects of interferons.
- Umut Sahin
- , Omar Ferhi
- & Valérie Lallemand-Breitenbach
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| Open AccessPredicting the risk of avian influenza A H7N9 infection in live-poultry markets across Asia
An avian influenza virus of the H7N9 type, associated with live-poultry markets, has caused two human epidemics in China. Here, the authors develop a statistical model that predicts the risk of H7N9 infection in live-poultry markets across Asia, as a tool for disease surveillance and control.
- Marius Gilbert
- , Nick Golding
- & Hongjie Yu
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Plasticity and redundancy among AMA–RON pairs ensure host cell entry of Toxoplasma parasites
Apicomplexan parasites such as Toxoplasma gondii and Plasmodium form a tight, moving junction with host cells before invading them. Here the authors show that the proteins AMA1 and RON2 of T. gondiicooperate during junction formation and identify additional proteins that have a role in this process.
- Mauld H. Lamarque
- , Magali Roques
- & Maryse Lebrun
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A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques
Helicobacter pylori chronically infects humans, and this is associated with high mutation and recombination rates in the bacterium. Here the authors provide evidence that genome evolution in H. pyloriduring acute infection of the host is orders of magnitude faster than any previously determined mutation rates in bacteria.
- Bodo Linz
- , Helen M. Windsor
- & Barry J. Marshall
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Membrane deformation and scission by the HSV-1 nuclear egress complex
Two viral proteins form the nuclear egress complex of herpesviruses, which is essential for the exit of nascent viral capsids from the cell nucleus. Here, the authors use synthetic lipid vesicles to show that the complex can mediate membrane budding in the absence of other cellular factors.
- Janna M. Bigalke
- , Thomas Heuser
- & Ekaterina E. Heldwein
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Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors
Histone-like HU proteins play roles in chromatin architecture and DNA-dependent processes in bacteria. Here, the authors describe the crystal structure of the DNA-binding domain of HU from Mycobacterium tuberculosis, and show that the pathogen’s growth can be inhibited using HU-targeting small molecules.
- Tuhin Bhowmick
- , Soumitra Ghosh
- & Valakunja Nagaraja
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| Open AccessEvidence of natural Wolbachia infections in field populations of Anopheles gambiae
Wolbachia bacteria live within the cells of many insect species, manipulating their hosts’ reproduction and immune responses. Here, the authors show that these microbes also infect wild populations of malaria-spreading Anopheles mosquitoes, supporting a potential use of Wolbachiato limit malaria transmission.
- Francesco Baldini
- , Nicola Segata
- & Flaminia Catteruccia
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Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection
Viral antigens can persist within the secondary lymphoid tissues of the host for many weeks after resolution of the infection. Tamburini et al.demonstrate that antigens remaining following viral infection or vaccination can be captured and maintained for extended periods of time by lymphatic endothelial cells.
- Beth A. Tamburini
- , Matthew A. Burchill
- & Ross M. Kedl
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| Open AccessPathogenic potential of interferon αβ in acute influenza infection
Interferon αβ(IFNαβ) is known as a potent anti-viral factor, yet its role in influenza infection remains controversial. Here, the authors show that the IFNαβ response is a critical host factor, which, when excessive, causes strong inflammation and severe disease in a mouse model of acute influenza infection.
- Sophia Davidson
- , Stefania Crotta
- & Andreas Wack
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Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment
The standard treatment for hepatitis C virus (HCV) infection, combining interferon (IFN) α and ribavirin, fails in a number of patients. Here, the authors use a mathematical model of the IFN signalling network in the presence of HCV to explain the success or failure of hepatitis C treatment.
- Pranesh Padmanabhan
- , Urtzi Garaigorta
- & Narendra M. Dixit
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| Open AccessA high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation
The human cytomegalovirus protein US11 downregulates host immune responses by redirecting HLA class I molecules for endoplasmic reticulum-associated protein degradation. Using a high-coverage genome-wide shRNA screen, the authors identify TMEM129 as an E3 ubiquitin ligase essential for this process.
- Michael L. van de Weijer
- , Michael C. Bassik
- & Robert Jan Lebbink