Featured
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| Open AccessLong-lasting renewable antibacterial porous polymeric coatings enable titanium biomaterials to prevent and treat peri-implant infection
Infection is a major problem for dental implants with current antibacterial coatings losing efficacy quickly. Here, the authors report on the N-halamine polymeric coating of titanium implants to create a long-lasting renewable antibacterial layer and demonstrate application in vivo.
- Shuyi Wu
- , Jianmeng Xu
- & Yan Li
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Article
| Open AccessRNA atlas of human bacterial pathogens uncovers stress dynamics linked to infection
Bacterial stress responses are potential targets for new antimicrobials. Here, Avican et al. present global transcriptomes for 32 bacterial pathogens grown under 11 stress conditions, and identify common and unique regulatory responses, as well as processes participating in different stress responses.
- Kemal Avican
- , Jehad Aldahdooh
- & Maria Fällman
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Article
| Open AccessInfant gut microbiome composition is associated with non-social fear behavior in a pilot study
Experimental manipulation of the gut microbiome in animal models impacts fear behaviours. Here, the authors show in a pilot study that features of the human infant gut microbiome are associated with non-social fear behaviours during a laboratory based assessment.
- Alexander L. Carlson
- , Kai Xia
- & Rebecca C. Knickmeyer
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Article
| Open AccessA unified route for flavivirus structures uncovers essential pocket factors conserved across pathogenic viruses
Understanding virus assembly could identify potential drug targets. Here the authors use a safe and efficient method to solve pathogenic flavivirus structures, revealing two lipid-like ligands within highly conserved pockets of the stem region of envelope protein that are important for virus maturation.
- Joshua M. Hardy
- , Natalee D. Newton
- & Daniel Watterson
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Article
| Open AccessImpact of COVID-19 outbreaks and interventions on influenza in China and the United States
Non-pharmaceutical interventions (NPIs) implemented to interrupt COVID-19 transmission may also impact the spread of other infectious diseases. Here, the authors estimate that influenza activity in China and the United States reduced by up to 80% when NPIs were in place in the 2019–2020 season.
- Luzhao Feng
- , Ting Zhang
- & George F. Gao
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Article
| Open AccessDesign of synthetic human gut microbiome assembly and butyrate production
Microbiomes designed with predictable functions could enable broad applications in health, agriculture and bioprocessing. Here the authors use a model-guided approach to design diverse synthetic human gut communities for production of the health-relevant metabolite butyrate.
- Ryan L. Clark
- , Bryce M. Connors
- & Ophelia S. Venturelli
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Article
| Open AccessStructure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer
Inositol hexakisphosphate (IP6) is a known assembly cofactor for HIV-1. Here, the authors show the role of IP6 in the assembly of the Rous sarcoma virus (RSV). Reported cryo-ET structures of mature capsid-like particles (CLPs) suggest that IP6 modulates the formation of capsid polyhedrons of variable shape.
- Martin Obr
- , Clifton L. Ricana
- & Robert A. Dick
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Article
| Open AccessGenome-resolved metagenomics reveals role of iron metabolism in drought-induced rhizosphere microbiome dynamics
Advances in omics provide a tool to understand mechanisms for plant–microbial interactions under stress. Here the authors apply genome-resolved metagenomics to investigate sorghum and its microbiome responses to drought, identifying an unexpected role of iron metabolism.
- Ling Xu
- , Zhaobin Dong
- & Devin Coleman-Derr
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Article
| Open AccessA sand fly salivary protein acts as a neutrophil chemoattractant
Immune mimicry has been shown in chemokine like moieties from bacteria and viruses. Here, the authors characterise a sand fly salivary protein that induces neutrophil chemotaxis and explore its impact in a model of parasitic infection.
- Anderson B. Guimaraes-Costa
- , John P. Shannon
- & Fabiano Oliveira
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Article
| Open AccessDynamic methylation of histone H3K18 in differentiating Theileria parasites
Post-translational modifications (PTM) of histones are important for epigenetic regulation in mammals. Here, Cheeseman et al. report dynamic changes in H3K18 PTM during the differentiation stages of Theileria parasites and they identify a SET-domain methyltransferase (TaSETup1) as the relevant enzyme promoting this modification.
- Kevin Cheeseman
- , Guillaume Jannot
- & Jonathan B. Weitzman
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Article
| Open AccessRationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis
Fecal microbiota transplantation and probiotics have been tested/used as potential therapeutics against inflammatory bowel diseases (IBD). Here the authors use a bottom-up rational consortium design approach that combines well-characterized strains isolated from healthy human stool samples to produce two consortia of metabolically interdependent strains for the treatment of IBD.
- Daniel van der Lelie
- , Akihiko Oka
- & R. Balfour Sartor
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Article
| Open AccessSmall sinking particles control anammox rates in the Peruvian oxygen minimum zone
Up to 40% of the ocean’s fixed nitrogen is lost in oxygen minimum zones (OMZs) by anammox, but despite the importance of this process, nitrogen loss patterns in OMZs are difficult to predict. Here the authors show that ammonium release from small particles is a major control of anammox in the Peruvian OMZ.
- Clarissa Karthäuser
- , Soeren Ahmerkamp
- & Marcel M. M. Kuypers
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Article
| Open AccessPareto optimality between growth-rate and lag-time couples metabolic noise to phenotypic heterogeneity in Escherichia coli
It is unclear how noise in gene expression propagates to phenotypic heterogeneity in clonal bacterial populations. Here, the authors explore how variability in central sugar metabolism in E. coli can mediate and promote population diversification.
- Diego Antonio Fernandez Fuentes
- , Pablo Manfredi
- & Mattia Zampieri
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Article
| Open AccessCompensatory evolution of Pseudomonas aeruginosa’s slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis
Long-term infection of cystic fibrosis patients with Pseudomonas aeruginosa is often accompanied by a reduction in bacterial growth rate. Here, La Rosa et al. use adaptive laboratory evolution to increase the growth rate of clinical isolates, and identify mechanisms and evolutionary trajectories that, in reverse direction, may help the pathogen to adapt to the patients’ airways.
- Ruggero La Rosa
- , Elio Rossi
- & Søren Molin
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Article
| Open AccessEffects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
There are currently no drugs available to treat SARS-CoV-2 infection. A promising alternative treatment for COVID-19 patients is convalescent plasma. Here, Gharbharan et al. collect covalescent plasma and report no overall clinical benefit for 86 patients hospitalized for COVID-19 and treated with 300 mL convalescent plasma.
- Arvind Gharbharan
- , Carlijn C. E. Jordans
- & Bart J. A. Rijnders
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Article
| Open AccessA single-cell atlas of Plasmodium falciparum transmission through the mosquito
Here the authors use single-cell RNA-seq to profile the transmission stages of the human malaria parasite Plasmodium falciparum as it progresses through the Anopheles mosquito. They highlight unique patterns of gene usage throughout this development and identify potential pleiotropic genes that function at multiple life cycle stages.
- Eliana Real
- , Virginia M. Howick
- & Mara K. N. Lawniczak
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Article
| Open AccessImmune response to SARS-CoV-2 variants of concern in vaccinated individuals
Here, the authors characterize the antibody response from vaccinated (Pfizer BNT-162b2), infected and uninfected individuals against emerging variants of concern of SARS-CoV-2, finding reduced neutralization of a South African isolate. High IgG titers in the saliva of vaccinees suggest that transmission may be reduced.
- Matthias Becker
- , Alex Dulovic
- & Nicole Schneiderhan-Marra
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Article
| Open AccessYeast cell fate control by temporal redundancy modulation of transcription factor paralogs
How dynamic transcription factors temporally interact to regulate stress survival in yeast is currently unclear. Here the authors integrate single-cell imaging, RNA-seq, and modeling to identify a new cell fate control mechanism mediated by temporal redundancy modulation during yeast stress response.
- Yan Wu
- , Jiaqi Wu
- & Yihan Lin
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Article
| Open AccessEcology and molecular targets of hypermutation in the global microbiome
Here, the authors report a large-scale comparative analysis of <30,000 Diversity-Generating Retroelements (DGRs) across ~9000 metagenomes (representing diverse taxa and biomes), to identify patterns in terms of prevalence and activity. Combined with examination of longitudinal data on <100 metagenomes part of time series, they demonstrate that DGRs are broadly and consistently active, implying an important role in microbiota ecology and evolution.
- Simon Roux
- , Blair G. Paul
- & Emiley A. Eloe-Fadrosh
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Article
| Open AccessStructural understanding of non-nucleoside inhibition in an elongating herpesvirus polymerase
Various herpesvirus therapeutics target the viral DNA polymerase. Here, the authors present the crystal structure of herpesvirus polymerase in the elongating state with bound primer-template DNA and the broad-spectrum non-nucleoside inhibitor PNU-183792, which is of interest for further drug design.
- Robert P. Hayes
- , Mee Ra Heo
- & Daniel Klein
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Article
| Open AccessMicrosecond fingerprint stimulated Raman spectroscopic imaging by ultrafast tuning and spatial-spectral learning
The authors employ a polygon-based ultrafast delay scanner and a deep learning framework for acquiring stimulated Raman scattering spectrum with high spectral and temporal resolution. They demonstrate high-speed imaging and tracking of multiple biomolecules in the fingerprint region.
- Haonan Lin
- , Hyeon Jeong Lee
- & Ji-Xin Cheng
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| Open AccessCryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins
Cortical microtubules (MTs) in Apicomplexa are specialized MTs involved in maintaining the parasite’s shape and are, as such, unusually stable. Here, cryo-EM analysis of cortical MTs from Toxoplasma gondii offers insight into the mechanism of their stabilization by three bona fide microtubule inner proteins.
- Xiangli Wang
- , Yong Fu
- & Rui Zhang
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Article
| Open AccessCryo-EM structure of the mature and infective Mayaro virus at 4.4 Å resolution reveals features of arthritogenic alphaviruses
Mayaro virus (MAYV) is an emerging arbovirus in Central and South America that is transmitted by mosquitoes and causes arthritogenic disease. Here, the authors present the 4.4 Å resolution cryo-EM structure of MAYV and describe specific features of the virus, which could be exploited for the design of MAYV-specific diagnostics and therapeutics.
- Helder V. Ribeiro-Filho
- , Lais D. Coimbra
- & Rafael Elias Marques
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Article
| Open AccessIdentification of microbial markers across populations in early detection of colorectal cancer
The gut microbiome plays an important role in colorectal carcinogenesis and predictive microbiome signatures have been proposed for colorectal cancer (CRC) diagnosis. Here the authors perform a meta-analysis of 16S rRNA-based profiles to identify microbial markers able to discriminate patients with adenoma from control and CRC, building a model that can be applied for the early detection of CRC.
- Yuanqi Wu
- , Na Jiao
- & Lixin Zhu
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Article
| Open AccessSevere T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes
Perturbed T cell responses and disturbed cytokine secretion have been shown during SARS-CoV2 infection in patients. Here the authors show reduced polyclonal T cell activity in COVID-19 patients that is caused by plasma factors and linked to poor prognosis and viral persistence.
- Kerstin Renner
- , Tobias Schwittay
- & Matthias Mack
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Article
| Open AccessTNF controls a speed-accuracy tradeoff in the cell death decision to restrict viral spread
Controlled cell death can be an efficient anti-viral strategy, but also leads to tissue damage and needs to be balanced. Oyler-Yaniv et al. combine mathematical modelling and microscopy to show that exposure to TNF in response to viral infection causes cells to tune their speed-vs-accuracy trade-off in cell death decision to limit HSV-1 spread.
- Jennifer Oyler-Yaniv
- , Alon Oyler-Yaniv
- & Roy Wollman
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Article
| Open AccessUSP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS
Ubiquitination has an important function in the regulation of antiviral immunity involving the signalling molecule MAVS. Here the authors investigate deubiquitinating enzymes and show USP18 regulates MAVS mediated antiviral signalling through modulating the ubiquitination of MAVS via promotion of interaction between MAVS and TRIM31.
- Jinxiu Hou
- , Lulu Han
- & Chengjiang Gao
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Article
| Open AccessSelf-association of MreC as a regulatory signal in bacterial cell wall elongation
MreC is a membrane-associated protein that modulates the activity of the elongasome, a protein complex that controls cell wall formation in rod-shaped bacteria. Here, the authors use electron cryo-microscopy and X-ray crystallography to determine the structure of a self-associated form of MreC in atomic detail.
- Alexandre Martins
- , Carlos Contreras-Martel
- & Andréa Dessen
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Article
| Open AccessCryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding
In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.
- Kaituo Wang
- , Robert Dagil
- & Ali Salanti
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Article
| Open AccessA trimethoprim derivative impedes antibiotic resistance evolution
The efficacy of the antibiotic trimethoprim, which inhibits bacterial dihydrofolate reductase (DHFR), is limited by the rapid emergence of resistant bacteria. Here, Manna et al. show that 4’-desmethyltrimethoprim inhibits DHFR and a common TMP-resistant variant, and impedes evolution of antibiotic resistance by selecting against the emergence of this variant.
- Madhu Sudan Manna
- , Yusuf Talha Tamer
- & Erdal Toprak
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Article
| Open AccessCross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection
Pre-existing immune responses between antigenically related viruses can influence responses in viral infections or vaccinations. Here the authors assess and characterize the presence of antibody and memory B cell populations specific to SARS-CoV2 and endemic human coronaviruses.
- Ge Song
- , Wan-ting He
- & Raiees Andrabi
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Article
| Open AccessMycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens
It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.
- Nicholas D. Walter
- , Sarah E. M. Born
- & Martin I. Voskuil
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Article
| Open AccessThe effect of generic market entry on antibiotic prescriptions in the United States
Generics contribute to increased availability of antibiotics, benefiting healthcare systems but potentially leading to increased consumption with implications for antibiotic stewardship and resistance. Here, the authors found no consistent changes in prescribing patterns of the 13 antibiotics that entered the US market as generics from 2000–2012.
- Cecilia Kållberg
- , Jemma Hudson
- & Ramanan Laxminarayan
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Article
| Open AccessPhospholipid translocation captured in a bifunctional membrane protein MprF
The Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. Here authors present cryo-electron microscopy structures of MprF homodimer from Rhizobium tropici (RtMprF) at two different states in complex with lysyl-phosphatidylglycerol (LysPG).
- Danfeng Song
- , Haizhan Jiao
- & Zhenfeng Liu
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Article
| Open AccessGene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators
Here, combing the massive gene-universe of the gut microbiome to identify strain-specific, cross-disease, associations across seven human diseases, the authors introduce the concept of microbiome architecture, defined as the complete set of positive and negative associations between microbial genes and human host disease, highlighting microbiome architectures as potential diagnostic indicators.
- Braden T. Tierney
- , Yingxuan Tan
- & Chirag J. Patel
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Article
| Open AccessFunctional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections
Although enterovirus D68 poses a major global threat to children, neither vaccines nor therapeutics are currently available. Using Cryo-EM, Zhang et al. show that two murine-derived monoclonal antibodies with therapeutic efficacy neutralize virions via binding to the canyon region, creating steric hindrance for sialic acid receptor binding.
- Chao Zhang
- , Cong Xu
- & Zhong Huang
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Article
| Open AccessToxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage
Apicomplexa generate essential lipids as combination of host fatty acids and de novo synthesized within the apicoplast. Here, the authors identify a phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as central for controlled lipid synthesis and define the host-scavenged lipidome.
- Sheena Dass
- , Serena Shunmugam
- & Cyrille Y. Botté
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Article
| Open AccessA global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch
Whole genome sequencing data are increasingly becoming routinely available but generating actionable insights is challenging. Here, the authors describe Pathogenwatch, a web tool for genomic surveillance of S. Typhi, and demonstrate its use for antimicrobial resistance assignment and strain risk assessment.
- Silvia Argimón
- , Corin A. Yeats
- & David M. Aanensen
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Article
| Open AccessIL-21 and IFNα therapy rescues terminally differentiated NK cells and limits SIV reservoir in ART-treated macaques
Infection of African green monkeys with SIV is associated with reduced pathogenicity. Here the authors explore the requirement of differentiated NK cell populations in a pathogenic Rhesus macaque model of SIV infection and show administration of IL-21 and IFNα rescues terminally differentiated NK cells, similarly to what found in African green monkeys, and limits the SIV reservoir in antiretroviral therapy treated macaques.
- Justin Harper
- , Nicolas Huot
- & Mirko Paiardini
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Article
| Open AccessLongitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection
The neurological effects of Ebola disease in the acute stage are not well-described. Here, the authors use longitudinal in vivo neuroimaging and immunohistochemistry to assess pathological changes in the central nervous system in a non-human primate model of Ebola virus infection.
- William Schreiber-Stainthorp
- , Jeffrey Solomon
- & Dima A. Hammoud
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Article
| Open AccessHeterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice
Heterologous vaccination regimens for COVID-19 could be useful for example if there is a shortage of one vaccine type. Here, Spencer et al. show that heterologous vaccination with a self-amplifying RNA vaccine and an adenoviral vectored vaccine performs at least as well as the homologous vaccinations in mice.
- Alexandra J. Spencer
- , Paul F. McKay
- & Teresa Lambe
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Article
| Open AccessCrystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions
SARS-CoV-2 orf9b binds to the mitochondrial outer membrane protein TOM70 and has been linked to the suppression of interferon responses. Here, the authors characterize the interactions of SARS-CoV-2 orf9b and human TOM70 biochemically, and they determine the 2.2 Å crystal structure of the TOM70 cytosolic domain with a bound SARS-CoV-2 orf9b peptide.
- Xiaopan Gao
- , Kaixiang Zhu
- & Sheng Cui
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Article
| Open AccessTargeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint
Shared metabolic pathways could allow simultaneous manipulation of T cells, viruses and tumours. Here the authors show targeting cholesterol esterification restrains hepatitis B in vitro, whilst bolstering exhausted antigen-specific T cell responses from human liver and hepatocellular carcinoma.
- Nathalie M. Schmidt
- , Peter A. C. Wing
- & Mala K. Maini
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Article
| Open AccessCharacterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein
The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.
- Pui Wang
- , Siu-Ying Lau
- & Honglin Chen
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Article
| Open AccessAnalysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection
Here the authors develop mosquito cell lines expressing Zika virus (ZIKV) capsid and perform proteomics experiments retrieving 157 protein interactors, of which they show 8 to act as pro-viral factors, showing the transitional endoplasmic reticulum 94 (TER94) and its human ortholog VCP target ZIKV capsid to proteasomal degradation to facilitate infection.
- Rommel J. Gestuveo
- , Jamie Royle
- & Margus Varjak
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Article
| Open AccessPlant DNA polymerases α and δ mediate replication of geminiviruses
Geminiviruses cause substantial damage to crops worldwide. Here Wu et al. show that geminivirus replication relies upon the host DNA polymerases α and δ, which produce double-stranded DNA intermediates and new copies of the viral genome, respectively, and is modulated by the viral C3 protein.
- Mengshi Wu
- , Hua Wei
- & Rosa Lozano-Durán
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Article
| Open AccessINI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
HIV-1 integrase (IN) binds the host factor INI1/SMARCB1, which is required at multiple stages of HIV-1 replication. Here, the authors show that the same IN residues are involved in INI1 and RNA binding and in influencing particle morphogenesis and suggest that the IN-binding INI1 domain is structurally similar to HIV TAR RNA.
- Updesh Dixit
- , Savita Bhutoria
- & Ganjam V. Kalpana
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Article
| Open AccessCommunity composition of microbial microcosms follows simple assembly rules at evolutionary timescales
Evolution affects microbial community composition, but it is still unknown how commonly compositions change, and how predictable such changes are. Using experimental evolution, Meroz et al. show that compositional changes typically occur within ~400 generations, and are predictable by a bottom-up approach.
- Nittay Meroz
- , Nesli Tovi
- & Jonathan Friedman
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Article
| Open AccessEstimating COVID-19 mortality in Italy early in the COVID-19 pandemic
Estimates of COVID-19-related mortality are limited by incomplete testing. Here, the authors perform counterfactual analyses and estimate that there were 59,000–62,000 deaths from COVID-19 in Italy until 9th September 2020, approximately 1.5 times higher than official statistics.
- Chirag Modi
- , Vanessa Böhm
- & Uroš Seljak
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