PLoS Biology最新文献

{"title":"Emergence of SARS-CoV-2 subgenomic RNAs that enhance viral fitness and immune evasion.","authors":"Harriet V Mears, George R Young, Theo Sanderson, Ruth Harvey, Jamie Barrett-Rodger, Rebecca Penn, Vanessa Cowton, Wilhelm Furnon, Giuditta De Lorenzo, Marg Crawford, Daniel M Snell, Ashley S Fowler, Anob M Chakrabarti, Saira Hussain, Ciarán Gilbride, Edward Emmott, Katja Finsterbusch, Jakub Luptak, Thomas P Peacock, Jérôme Nicod, Arvind H Patel, Massimo Palmarini, Emma Wall, Bryan Williams, Sonia Gandhi, Charles Swanton, David L V Bauer","doi":"10.1371/journal.pbio.3002982","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002982","url":null,"abstract":"<p><p>Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages. The most frequent neo-TRS is within the coding region of the Nucleocapsid gene, and is present in virtually all viruses from the B.1.1 lineage, including the variants of concern Alpha, Gamma, Omicron and descendants thereof. Here, we demonstrate that this TRS leads to the expression of a novel subgenomic mRNA encoding a truncated C-terminal portion of Nucleocapsid, which is an antagonist of type I interferon production and contributes to viral fitness during infection. We observe distinct phenotypes when the Nucleocapsid coding sequence is mutated compared to when the TRS alone is ablated. Our findings demonstrate that SARS-CoV-2 is undergoing evolutionary changes at the functional RNA level in addition to the amino acid level.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002982"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Language-specific neural dynamics extend syntax into the time domain.","authors":"Cas W Coopmans, Helen de Hoop, Filiz Tezcan, Peter Hagoort, Andrea E Martin","doi":"10.1371/journal.pbio.3002968","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002968","url":null,"abstract":"<p><p>Studies of perception have long shown that the brain adds information to its sensory analysis of the physical environment. A touchstone example for humans is language use: to comprehend a physical signal like speech, the brain must add linguistic knowledge, including syntax. Yet, syntactic rules and representations are widely assumed to be atemporal (i.e., abstract and not bound by time), so they must be translated into time-varying signals for speech comprehension and production. Here, we test 3 different models of the temporal spell-out of syntactic structure against brain activity of people listening to Dutch stories: an integratory bottom-up parser, a predictive top-down parser, and a mildly predictive left-corner parser. These models build exactly the same structure but differ in when syntactic information is added by the brain-this difference is captured in the (temporal distribution of the) complexity metric \"incremental node count.\" Using temporal response function models with both acoustic and information-theoretic control predictors, node counts were regressed against source-reconstructed delta-band activity acquired with magnetoencephalography. Neural dynamics in left frontal and temporal regions most strongly reflect node counts derived by the top-down method, which postulates syntax early in time, suggesting that predictive structure building is an important component of Dutch sentence comprehension. The absence of strong effects of the left-corner model further suggests that its mildly predictive strategy does not represent Dutch language comprehension well, in contrast to what has been found for English. Understanding when the brain projects its knowledge of syntax onto speech, and whether this is done in language-specific ways, will inform and constrain the development of mechanistic models of syntactic structure building in the brain.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002968"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced alterations in behaviour.","authors":"Anna Jász, László Biró, Zsolt Buday, Bálint Király, Orsolya Szalárdy, Krisztina Horváth, Gergely Komlósi, Róbert Bódizs, Krisztina J Kovács, Marco A Diana, Balázs Hangya, László Acsády","doi":"10.1371/journal.pbio.3002962","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002962","url":null,"abstract":"<p><p>A single exposure to a stressful event can result in enduring changes in behaviour. Long-term modifications in neuronal networks induced by stress are well explored but the initial steps leading to these alterations remain incompletely understood. In this study, we found that acute stress exposure triggers an immediate increase in the firing activity of calretinin-positive neurons in the paraventricular thalamic nucleus (PVT/CR+) that persists for several days in mice. This increase in activity had a causal role in stress-induced changes in spontaneous behaviour. Attenuating PVT/CR+ neuronal activity for only 1 h after the stress event rescued both the protracted increase in PVT/CR+ firing rate and the stress-induced behavioural alterations. Activation of the key forebrain targets (basolateral amygdala, prelimbic cortex, and nucleus accumbens) that mediate defensive behaviour has also been reduced by this post-stress inhibition. Reduction of PVT/CR+ cell activity 5 days later remained still effective in ameliorating stress-induced changes in spontaneous behaviour. The results demonstrate a critical role of the prolonged, post-stress changes in firing activity of PVT/CR+ neurons in shaping the behavioural changes associated with stress. Our data proposes a therapeutic window for intervention in acute stress-related disorders, offering potential avenues for targeted treatment strategies.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002962"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.","authors":"Lavisha Parab, Jordan Romeyer Dherbey, Norma Rivera, Michael Schwarz, Jenna Gallie, Frederic Bertels","doi":"10.1371/journal.pbio.3002952","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002952","url":null,"abstract":"<p><p>Bacteriophages infect gram-negative bacteria by attaching to molecules present on the bacterial surface, often lipopolysaccharides (LPS). Modification of LPS can lead to resistance to phage infection. In addition, LPS modifications can impact antibiotic susceptibility, allowing for phage-antibiotic synergism. The evolutionary mechanism(s) behind such synergistic interactions remain largely unclear. Here, we show that the presence of antibiotics can affect the evolution of resistance to phage infection, using phage ΦX174 and Escherichia coli C. We use a collection of 34 E. coli C LPS strains, each of which is resistant to ΦX174, and has either a \"rough\" or \"deep rough\" LPS phenotype. Growth of the bacterial strains with the deep rough phenotype is inhibited at low concentrations of chloramphenicol and, to a much lesser degree, gentamicin. Treating E. coli C wild type with ΦX174 and chloramphenicol eliminates the emergence of mutants with the deep rough phenotype, and thereby slows the evolution of resistance to phage infection. At slightly lower chloramphenicol concentrations, phage resistance rates are similar to those observed at high concentrations; yet, we show that the diversity of possible mutants is much larger than at higher chloramphenicol concentrations. These data suggest that specific antibiotic concentrations can lead to synergistic phage-antibiotic interactions that disappear at higher antibiotic concentrations. Overall, we show that the change in survival of various ΦX174-resistant E. coli C mutants in the presence of antibiotics can explain the observed phage-antibiotic synergism.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002952"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral and immune dynamics of genital human papillomavirus infections in young women with high temporal resolution.","authors":"Nicolas Tessandier, Baptiste Elie, Vanina Boué, Christian Selinger, Massilva Rahmoun, Claire Bernat, Sophie Grasset, Soraya Groc, Anne-Sophie Bedin, Thomas Beneteau, Marine Bonneau, Christelle Graf, Nathalie Jacobs, Tsukushi Kamiya, Marion Kerioui, Julie Lajoie, Imène Melki, Jean-Luc Prétet, Bastien Reyné, Géraldine Schlecht-Louf, Mircea T Sofonea, Olivier Supplisson, Chris Wymant, Vincent Foulongne, Jérémie Guedj, Christophe Hirtz, Marie-Christine Picot, Jacques Reynes, Vincent Tribout, Édouard Tuaillon, Tim Waterboer, Michel Segondy, Ignacio G Bravo, Nathalie Boulle, Carmen Lía Murall, Samuel Alizon","doi":"10.1371/journal.pbio.3002949","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002949","url":null,"abstract":"<p><p>Human papillomavirus (HPV) infections drive one in 20 new cancer cases, exerting a particularly high burden on women. Most anogenital HPV infections are cleared in less than two years, but the underlying mechanisms that favour persistence in around 10% of women remain largely unknown. Notwithstanding, it is precisely this information that is crucial for improving treatment, screening, and vaccination strategies. To understand viral and immune dynamics in non-persisting HPV infections, we set up an observational longitudinal cohort study with frequent on-site visits for biological sample collection. We enrolled 189 women aged from 18 to 25 and living in the area of Montpellier (France) between 2016 and 2020. We performed 974 on-site visits for a total of 1,619 months of follow-up. We collected data on virus load, local immune cell populations, local concentrations of cytokines, and circulating antibody titres. Using hierarchical Bayesian statistical modelling to simultaneously analyse the data from 164 HPV infections from 76 participants, we show that in two months after infection, HPV viral load in non-persisting infections reaches a plateau that lasts on average for 13 to 20 months (95% credibility interval) and is then followed by a rapid clearance phase. This first description of the dynamics of HPV infections comes with the identification of immune correlates associated with infection clearance, especially gamma-delta T cells and CXCL10 concentration. A limitation of this study on HPV kinetics is that many infection follow-ups are censored. Furthermore, some immune cell populations are difficult to label because cervical immunity is less well characterised than systemic immunity. These results open new perspectives for understanding the frontier between acute and chronic infections, and for controlling HPV-associated diseases, as well as for research on human cancers of infectious origin. Trial Registration: This trial was registered is registered at ClinicalTrials.gov under the ID NCT02946346. This study has been approved by the Comité de Protection des Personnes (CPP) Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/ AR1612278, decision number DR-2016-488), by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007).</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002949"},"PeriodicalIF":9.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous slow cortical potentials and brain oscillations independently influence conscious visual perception.","authors":"Lua Koenig, Biyu J He","doi":"10.1371/journal.pbio.3002964","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002964","url":null,"abstract":"<p><p>Perceptual awareness results from an intricate interaction between external sensory input and the brain's spontaneous activity. Pre-stimulus ongoing activity influencing conscious perception includes both brain oscillations in the alpha (7 to 14 Hz) and beta (14 to 30 Hz) frequency ranges and aperiodic activity in the slow cortical potential (SCP, <5 Hz) range. However, whether brain oscillations and SCPs independently influence conscious perception or do so through shared mechanisms remains unknown. Here, we addressed this question in 2 independent magnetoencephalography (MEG) data sets involving near-threshold visual perception tasks in humans using low-level (Gabor patches) and high-level (objects, faces, houses, animals) stimuli, respectively. We found that oscillatory power and large-scale SCP activity influence conscious perception through independent mechanisms that do not have shared variance. In addition, through mediation analysis, we show that pre-stimulus oscillatory power and SCP activity have different relations to pupil size-an index of arousal-in their influences on conscious perception. Together, these findings suggest that oscillatory power and SCPs independently contribute to perceptual awareness, with distinct relations to pupil-linked arousal.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002964"},"PeriodicalIF":9.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How can modeling responsibly inform decision-making in malaria?","authors":"Jaline Gerardin, Melissa A Penny","doi":"10.1371/journal.pbio.3002991","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002991","url":null,"abstract":"<p><p>When models are used to inform decision-making, both their strengths and limitations must be considered. Using malaria as an example, we explain how and why models are limited and offer guidance for ensuring a model is well-suited for its intended purpose.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002991"},"PeriodicalIF":9.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards ensuring reproducibility of outsourced data generation.","authors":"Daniel B Sloan, Mark D Stenglein","doi":"10.1371/journal.pbio.3002988","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002988","url":null,"abstract":"<p><p>\"Big data\" generated from outsourced or centralized facilities often lacks methodological information. Here, we outline how and why researchers, service providers, and other parties should report on methodology and sample metadata to improve scientific reproducibility.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002988"},"PeriodicalIF":9.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-tissue characterization of the constitutive heterochromatin proteome in Drosophila identifies a link between satellite DNA organization and transposon repression.","authors":"Ankita Chavan, Lena Skrutl, Federico Uliana, Melanie Pfister, Franziska Brändle, Laszlo Tirian, Delora Baptista, Dominik Handler, David Burke, Anna Sintsova, Pedro Beltrao, Julius Brennecke, Madhav Jagannathan","doi":"10.1371/journal.pbio.3002984","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002984","url":null,"abstract":"<p><p>Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized. Here, we use 2 satellite DNA-binding proteins, D1 and Prod, as baits to characterize the chromocenter-associated proteome in Drosophila embryos, ovaries, and testes through quantitative mass spectrometry. We identify D1- and Prod-associated proteins, including known heterochromatin proteins as well as proteins previously unlinked to satellite DNA or chromocenters, thereby laying the foundation for a comprehensive understanding of cellular functions enabled by satellite DNA repeats and their associated proteins. Interestingly, we find that multiple components of the transposon-silencing piRNA pathway are associated with D1 and Prod in embryos. Using genetics, transcriptomics, and small RNA profiling, we show that flies lacking D1 during embryogenesis exhibit transposon expression and gonadal atrophy as adults. We further demonstrate that this gonadal atrophy can be rescued by mutating the checkpoint kinase, Chk2, which mediates germ cell arrest in response to transposon mobilization. Thus, we reveal that a satellite DNA-binding protein functions during embryogenesis to silence transposons, in a manner that is heritable across later stages of development.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002984"},"PeriodicalIF":9.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dorsal hippocampus represents locations to avoid as well as locations to approach during approach-avoidance conflict.","authors":"Olivia L Calvin, Matthew T Erickson, Cody J Walters, A David Redish","doi":"10.1371/journal.pbio.3002954","DOIUrl":"10.1371/journal.pbio.3002954","url":null,"abstract":"<p><p>Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta cycles. Similarly, important information that is distant from the animal's position is represented during hippocampal high-synchrony events (HSEs), which coincide with sharp-wave ripples (SWRs). It is likely that potential future threats may be similarly represented. We examined how threats and rewards were represented within the hippocampus during approach-avoidance conflicts in rats faced with a predator-like robot guarding a food reward. We found decoding of the pseudo-predator's location during HSEs when hesitating in the nest and during theta prior to retreating as the rats approached the pseudo-predator. After the first attack, we observed new place fields appearing at the location of the robot (not the location the rat was when attacked). The anxiolytic diazepam reduced anxiety-like behavior and altered hippocampal local field potentials (LFPs), including reducing SWRs, suggesting that one potential mechanism of diazepam's actions may be through altered representations of imagined threat. These results suggest that hippocampal representation of potential threats could be an important mechanism that underlies worry and a potential target for anxiolytics.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002954"},"PeriodicalIF":9.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}