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| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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Article
| Open AccessBat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets
In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.
- Nico Joel Halwe
- , Lea Hamberger
- & Martin Beer
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| Open AccessCross-species spill-over potential of the H9N2 bat influenza A virus
In this study, the authors report that a bat influenza A (H9N2) virus shows receptor binding features similar to avian influenza viruses, efficiently infects ex-vivo human respiratory cells and replicates in the lungs of mice and upper respiratory tract of ferrets following airborne transmission.
- Rabeh El-Shesheny
- , John Franks
- & Richard J. Webby
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| Open AccessSynergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection
In this study, the authors show that a single dose of a combination of two human-like monoclonal antibodies protect mice in therapeutic treatment against challenges with ectromelia virus and monkeypox virus. Combination treatment provided more effective viral clearance than single antibody treatment.
- Hadas Tamir
- , Tal Noy-Porat
- & Tomer Israely
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Article
| Open AccessPrior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses
Co-infections are much less studied than single pathogen infections. Here, the authors show that co-infection with two unrelated viruses, neurotropic Semliki Forest virus and influenza A virus, exacerbates influenza-related lung pathology and prolongs lung virus replication in a mouse model.
- Isabelle Jia-Hui Foo
- , Brendon Y. Chua
- & Lukasz Kedzierski
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Article
| Open AccessInhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2
Inhibiting SARS-CoV-2 interaction with ACE2 is a promising antiviral strategy. Here, the authors show that exosomes derived from human lung spheroid cells expressing hACE2 accumulate in the lung following prophylactic inhalation to bind and neutralize SARS-CoV-2 and protect mice from SARS-CoV-2-induced disease.
- Zhenzhen Wang
- , Shiqi Hu
- & Ke Cheng
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Article
| Open AccessNeuronal miR-9 promotes HSV-1 epigenetic silencing and latency by repressing Oct-1 and Onecut family genes
Here, the authors identify neuron-specific miR-9 that potentially blocks HSV-1 neuronal replication by targeting host OCT-1 and ONECUT transcription factors involved in epigenetic activation of HSV-1 productive-cycle genes. Thus miR-9 promotes viral epigenetic silencing and latent infection in neurons.
- Yue Deng
- , Yuqi Lin
- & Dongli Pan
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Article
| Open AccessA humanized mouse model for adeno-associated viral gene therapy
All natural AAV serotypes transduce murine hepatocytes more efficiently than their human counterparts in human liver chimeric mouse models. Here the authors developed a novel humanized mouse were human transduction of AAV can be studied.
- Mercedes Barzi
- , Tong Chen
- & Karl-Dimiter Bissig
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Article
| Open AccessNucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus
There are limited treatment options for infection with Crimean-Congo hemorrhagic fever virus in humans. Here, the authors show that a monoclonal antibody targeting the highly conserved viral nucleocapsid protein provides protective effects in a mouse model of infection.
- Aura R. Garrison
- , Vanessa Moresco
- & Joseph W. Golden
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Article
| Open AccessDrug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor
There is a need for effective antiviral drugs against RSV infection. Conducting an RSV repurposing screen using the ReFRAME library Sake et al. identify lonafarnib as an RSV fusion protein inhibitor, characterize its binding site within the viral protein and show its antiviral effects in a mouse model.
- Svenja M. Sake
- , Xiaoyu Zhang
- & Thomas Pietschmann
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| Open AccessIsolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice
Pangolins are a potential reservoir for viruses with cross-species infection potential. Here, the authors characterize a HKU4-related coronavirus isolated from pangolin and demonstrate its ability to infect human cell lines as well as its potential to infect transgenic mice expressing the human receptor DPP4.
- Luo-Yuan Xia
- , Zhen-Fei Wang
- & Wu-Chun Cao
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Article
| Open AccessIdentification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants
Most recent SARS-CoV-2 variants showed exceptional immune evasion properties. Here, the authors identify a highly conserved epitope within the RBD targeted by a broad spectrum neutralizing antibody BA7535 that shows therapeutic antiviral potency in mouse studies.
- Yanqun Wang
- , An Yan
- & Jincun Zhao
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Article
| Open AccessHuman coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice
The origin of SARS-CoV-2 cross-reactive T cells in unexposed humans is unclear. Here, the authors use HLA transgenic mouse models of sequential infections with human coronavirus OC43 and SARSCoV-2 and show that OC43 elicits cross-protective immunity against SARS-CoV-2, which partially depends on CD4 + T cells.
- Rúbens Prince dos Santos Alves
- , Julia Timis
- & Sujan Shresta
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Article
| Open AccessAncient diversity in host-parasite interaction genes in a model parasitic nematode
Host-parasite interactions can lead to negative frequency-dependent selection. Here, the authors sequence the genomes of H. bakeri and H. polygyrus, parasites of house and wood mice, respectively, and find that proteins that interact with the host immune response are often highly diverse.
- Lewis Stevens
- , Isaac Martínez-Ugalde
- & Mark Blaxter
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Article
| Open AccessFHL1 promotes chikungunya and o’nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design
FHL1A is a crucial host factor for alphavirus infection but its impact on pathogenesis is unclear. Here, the authors use a FHL1−/− knockout mouse model to show that the FHL1 splice variant impacts arthritis and myositis after chikungunya or o’nyong-nyong infections but not Ross River or mayaro virus infection.
- Wern Hann Ng
- , Xiang Liu
- & Suresh Mahalingam
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Article
| Open AccessIDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
The role of human glioma IDH1 mutations in regulation of antiviral response is unclear. Here, the authors show that D2HG produced by mutant IDH1 inhibits IFN antiviral responses in glioma cells, which confers sensitivity to oncolytic virotherapy.
- Xueqin Chen
- , Jun Liu
- & Haipeng Zhang
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Article
| Open AccessAn interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models
Here, the authors report the generation of a live but defective SARS-CoV-2 virus that is envelope-deficient and expresses human interferon beta. They show that nasal vaccination enhances mucosal and lung T cell response and provides pan-sarbecovirus protection in small animals.
- Chun-Kit Yuen
- , Wan-Man Wong
- & Kin-Hang Kok
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Article
| Open AccessmRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
The authors report mRNA vaccines encoding a fusion protein of MPXV A35R extracellular domain and full-length M1R and observe improved anti-M1R antibody response. The vaccines show enhanced active and passive protection in female mice challenged with a lethal dose of vaccinia virus.
- Fujun Hou
- , Yuntao Zhang
- & Xiaoming Yang
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Article
| Open AccessMAVS signaling is required for preventing persistent chikungunya heart infection and chronic vascular tissue inflammation
Mosquito-borne viruses are serious global public health threats associated with severe atypical cardiovascular manifestations. Here, the authors dissect how chikungunya virus directly infects cardiac tissue leading to heart disease and define key host pathways involved in viral cardiac persistence and tissue damage.
- Maria G. Noval
- , Sophie N. Spector
- & Kenneth A. Stapleford
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Article
| Open AccessTagging active neurons by soma-targeted Cal-Light
Techniques for tagging active neurons with high spatiotemporal precision are limited. Here the authors report soma-targeted CalLight (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression, and generate a conditional ST-Cal-Light knock-in mouse.
- Jung Ho Hyun
- , Kenichiro Nagahama
- & Hyung-Bae Kwon
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Article
| Open AccessSex differences in allometry for phenotypic traits in mice indicate that females are not scaled males
Research aimed at improving healthcare has largely focused on male animals and cells. Here, the authors use data from the International Mouse Phenotyping Consortium to show that body weight does not account for all phenotypic differences between male and female mice, supporting more female-focused research.
- Laura A. B. Wilson
- , Susanne R. K. Zajitschek
- & Shinichi Nakagawa
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Article
| Open AccessHypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia
Developing brain-protective hypothermia is a medical challenge. Here, the authors show that deep brain stimulation of a particular brain area is a new way to trigger the body into a hibernation-like state with reduced body temperature and brain protection in a mouse model of stroke.
- Shuai Zhang
- , Xinpei Zhang
- & Sheng-Tao Hou
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Article
| Open AccessA doxycycline- and light-inducible Cre recombinase mouse model for optogenetic genome editing
Achieving spatial control of gene expression is important. Here the authors report an optimised photoactivatable Cre recombinase system, doxycycline- and light-inducible Cre recombinase (DiLiCre), and generate a DiLiCre mouse line which they use for mutagenesis in vivo and positional cell-tracing.
- Miguel Vizoso
- , Colin E. J. Pritchard
- & Jacco van Rheenen
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Article
| Open AccessOptogenetic manipulation and photoacoustic imaging using a near-infrared transgenic mouse model
Optogenetic tools can be used as in vivo imaging probes. Here the authors generate a loxP-BphP1 transgenic mouse to enable Cre-dependent temporal and spatial targeting of BphP1 expression in vivo; they show photoacoustic tomography of BphP1 expression in developing embryos and regenerating livers.
- Ludmila A. Kasatkina
- , Chenshuo Ma
- & Vladislav V. Verkhusha
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Article
| Open AccessDynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice
The in vivo identification of proteins secreted from a specific cell type or tissue remains challenging. Here, the authors develop a proximity labeling-based method to selectively label secreted proteins and combine it with proteomics to identify liver secretory proteins in mouse plasma.
- Kwang-eun Kim
- , Isaac Park
- & Jae Myoung Suh
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Article
| Open AccessCoordination of endothelial cell positioning and fate specification by the epicardium
It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.
- Pearl Quijada
- , Michael A. Trembley
- & Eric M. Small
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Article
| Open AccessAn original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing
Bacterial and fungal pathogens that cross the blood-brain-barrier (BBB) can cause severe disease. Here, Benmimoun et al. develop a model to study BBB crossing in the developing Drosophila brain and discover Group B Streptococcus factors important for BBB crossing and virulence, one of which, a lipoprotein, they confirm in mice.
- Billel Benmimoun
- , Florentia Papastefanaki
- & Pauline Spéder
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Article
| Open AccessVav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis
Skeletal muscle plays a key role in regulating systemic glucose and metabolic homeostasis. Here, the authors show that the catalytic activity of Vav2, an activator of Rho GTPases, modulates those processes by favoring the responsiveness of this tissue to insulin and related factors.
- Sonia Rodríguez-Fdez
- , L. Francisco Lorenzo-Martín
- & Xosé R. Bustelo
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Article
| Open AccessTranscriptional activity and strain-specific history of mouse pseudogenes
Pseudogenes are key markers of genome remodelling processes. Here the authors present genome-wide annotation of the pseudogenes in the mouse reference genome and 18 inbred mouse strains, update human pseudogene annotations, and characterise the transcription and evolution of mouse pseudogenes.
- Cristina Sisu
- , Paul Muir
- & Mark Gerstein
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Article
| Open AccessA HaloTag-TEV genetic cassette for mechanical phenotyping of proteins from tissues
Testing mechanical forces on native molecules in natural environments remains a challenge. Here the authors engineer titin to carry a HaloTag-TEV insertion to allow analysis of dynamics under force in muscle fibers.
- Jaime Andrés Rivas-Pardo
- , Yong Li
- & Jorge Alegre-Cebollada
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Article
| Open AccessCep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions
In mammalian cell lines, Cep55 protein recruits the endosomal sorting complex required for transport (ESCRT) and promotes the completion of cell division. Here, the authors show that Cep55-knockout mice are viable and primary fibroblasts cultured in vitro divide in a Cep55 and ESCRT-independent way.
- Antonio Tedeschi
- , Jorge Almagro
- & Mark Petronczki
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Article
| Open AccessThe autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
In humans, copy-number variants of the CYFIP1 gene have been associated with autism spectrum disorders and schizophrenia. Here, the authors characterize Cyfip1-heterozygous mice, revealing that they display deficits in brain white matter structure and functional connectivity along with abnormal behaviours.
- Nuria Domínguez-Iturza
- , Adrian C. Lo
- & Claudia Bagni
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Article
| Open AccessZnhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation
Lgr5+ stem cells in intestinal crypts are critical for gut epithelium homeostasis. Here, the authors show that Znht1 critically regulates intestinal homeostasis by promoting interaction between histone variant H2A.Z and its chaperone YL1 to incorporate H2A.Z into genes involved in intestinal stem cell fate.
- Bing Zhao
- , Ying Chen
- & Xinhua Lin
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Article
| Open AccessPrevalence of sexual dimorphism in mammalian phenotypic traits
Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.
- Natasha A. Karp
- , Jeremy Mason
- & Jacqueline K. White
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Article
| Open AccessNovel gene function revealed by mouse mutagenesis screens for models of age-related disease
Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.
- Paul K. Potter
- , Michael R. Bowl
- & Steve D. M. Brown
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Article
| Open Accessβ-Catenin C-terminal signals suppress p53 and are essential for artery formation
How p53 is restrained in arterial maturation during embryonic development is unclear. Here, the authors show that β-catenin C-terminal interactions inhibit CREB binding protein-mediated acetylation and activation of p53 in smooth muscle cells, and that this function is essential for artery formation.
- Dario F. Riascos-Bernal
- , Prameladevi Chinnasamy
- & Nicholas E. S. Sibinga
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Article
| Open AccessA mouse model for a partially inactive obesity-associated human MC3R variant
The melanocortin receptor, MC3R, regulates organismal energy homeostasis. Here, Lee et al. create knock-in mice with the a mutated version of the human MC3R receptor found in obese children, and show these mice have more fat and smaller bone, yet are by and large metabolically healthy.
- Bonggi Lee
- , Jashin Koo
- & Jack A. Yanovski
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Article
| Open AccessMouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function
Beige adipocytes are formed in response to cold and thought to contribute to organismal energy homeostasis. Here, the authors study a range of conditional and inducible RFP-expressing Cre mouse strains and find that SMA-based lines are the most useful for mapping beige adipocyte progenitor cells.
- Daniel C. Berry
- , Yuwei Jiang
- & Jonathan M. Graff
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Efficient genome engineering by targeted homologous recombination in mouse embryos using transcription activator-like effector nucleases
Genetically engineered mice are an important aspect of human disease research. Here, the authors use artificial transcription activator-like effector-nucleases to generate a mouse line with a conditionally targeted allele and suggest that this method can be easily adapted to any gene in the mouse genome.
- Daniel Sommer
- , Annika E. Peters
- & Marc Beyer
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Article |
A mouse model of adult-onset anaemia due to erythropoietin deficiency
Kidney diseases often cause anaemia due to damage of renal erythropoietin-producing cells. Yamazaki et al. identify a new population of erythropoietin-producing cells in the renal cortex and outer medulla by establishing a mouse model for adult-onset erythropoietin-deficient anaemia.
- Shun Yamazaki
- , Tomokazu Souma
- & Masayuki Yamamoto
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Article
| Open AccessA chronic model of arthritis supported by a strain-specific periarticular lymph node in BALB/c mice
Mouse models of arthritis generally do not result in both chronic disease and autoantibody production—two key features of the human disease. Here the authors obtain both features by combining two common protocols, and find that disease severity is associated with the presence of a previously unidentified lymph node.
- Uta Baddack
- , Sven Hartmann
- & Gerd Müller