mBio最新文献

{"title":"Machine learning reveals the dynamic importance of accessory sequences for <i>Salmonella</i> outbreak clustering.","authors":"Chao Chun Liu, William W L Hsiao","doi":"10.1128/mbio.02650-24","DOIUrl":"10.1128/mbio.02650-24","url":null,"abstract":"<p><p>Bacterial typing at whole-genome scales is now feasible owing to decreasing costs in high-throughput sequencing and the recent advances in computation. The unprecedented resolution of whole-genome typing is achieved by genotyping the variable segments of bacterial genomes that can fluctuate significantly in gene content. However, due to the transient and hypervariable nature of many accessory elements, the value of the added resolution in outbreak investigations remains disputed. To assess the analytical value of bacterial accessory genomes in clustering epidemiologically related cases, we trained classifiers on a set of genomes collected from 24 <i>Salmonella enterica</i> outbreaks of food, animal, or environmental origin. The models demonstrated high precision and recall on unseen test data with near-perfect accuracy in classifying clonal and short-term outbreaks. Annotating the genomic features important for cluster classification revealed functional enrichment of molecular fingerprints in genes involved in membrane transportation, trafficking, and carbohydrate metabolism. Importantly, we discovered polymorphisms in mobile genetic elements (MGEs) and gain/loss of MGEs to be informative in defining outbreak clusters. To quantify the ability of MGE variations to cluster outbreak clones, we devised a reference-free tree-building algorithm inspired by colored de Bruijn graphs, which enabled topological comparisons between MGE and standard typing methods. Systematic evaluation of clustering MGEs on an unseen dataset of 34 <i>Salmonella</i> outbreaks yielded mixed results that exemplified the power of accessory sequence variations when core genomes of unrelated cases are insufficiently discriminatory, as well as the distortion of outbreak signals by microevolution events or the incomplete assembly of MGEs.</p><p><strong>Importance: </strong>Gene-by-gene typing is widely used to detect clusters of foodborne illnesses that share a common origin. It remains actively debated whether the inclusion of accessory sequences in bacterial typing schema is informative or deleterious for cluster definitions in outbreak investigations due to the potential confounding effects of horizontal gene transfer. By training machine learning models on a curated set of historical <i>Salmonella</i> outbreaks, we revealed an enriched presence of outbreak distinguishing features in a wide range of mobile genetic elements. Systematic comparison of the efficacy of clustering different accessory elements against standard sequence typing methods led to our cataloging of scenarios where accessory sequence variations were beneficial and uninformative to resolving outbreak clusters. The presented work underscores the complexity of the molecular trends in enteric outbreaks and seeks to inspire novel computational ways to exploit whole-genome sequencing data in enteric disease surveillance and management.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0265024"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052978","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":"Identification of intratumoral bacteria that enhance breast tumor metastasis.","authors":"Zachary J Gerbec, Antonio Serapio-Palacios, Avril Metcalfe-Roach, Zakhar Krekhno, Haggai Bar-Yoseph, Sarah E Woodward, Jorge Pena-Díaz, Oksana Nemirovsky, Shannon Awrey, Sebastian H Moreno, Sean Beatty, Esther Kong, Nina Radisavljevic, Mihai Cirstea, Shawn Chafe, Paul C McDonald, Sam Aparicio, B Brett Finlay, Shoukat Dedhar","doi":"10.1128/mbio.03595-24","DOIUrl":"10.1128/mbio.03595-24","url":null,"abstract":"<p><p>The central, mortality-associated hallmark of cancer is the process of metastasis. It is increasingly recognized that bacteria influence multiple facets of cancer progression, but the extent to which tumor microenvironment-associated bacteria control metastasis in cancer is poorly understood. To identify tumor-associated bacteria and their role in metastasis, we utilized established murine models of non-metastatic and metastatic breast tumors to identify bacteria capable of driving metastatic disease. We found several species of the <i>Bacillus</i> genus that were unique to metastatic tumors, and found that breast tumor cells cultured with a <i>Bacillus</i> bacterium isolated from metastatic tumors, <i>Bacillus thermoamylovorans</i>, produced nearly 3× the metastatic burden as control cells or cells cultured with bacteria from non-metastatic breast tumors. We then performed targeted metabolomics on tumor cells cultured with different bacterial species and found that <i>B. thermoamylovorans</i> differentially regulated tumor cell metabolite profiles compared to bacteria isolated from non-metastatic tumors. Using these bacteria, we performed <i>de novo</i> sequencing and tested for the presence of genes that were unique to the bacterium isolated from metastatic tumors in a patient population to provide a proof-of-concept for identifying how specific bacterial functions are associated with the metastatic process in cancer independent of bacterial species. Together, our data directly demonstrate the ability of specific bacteria to promote metastasis through interaction with cancer cells.</p><p><strong>Importance: </strong>Metastasis is a major barrier to long-term survival for cancer patients, and therapeutic options for patients with aggressive, metastatic forms of breast cancer remain limited. It is therefore critical to understand the differences between non-metastatic and metastatic disease to identify potential methods for slowing or even stopping metastasis. In this work, we identify a bacterial species present with metastatic breast tumors capable of increasing the metastatic capabilities of tumor cells. We isolated and sequenced this bacteria, as well as a control species which failed to promote metastasis, and identified specific bacterial genes that were unique to the metastasis-promoting species. We tested for the presence of these bacterial genes in patient tumor samples and found they were more likely to be associated with mortality. We also identified enrichment of specific bacterial functions, providing insight into possible sources of bacteria-driven increases in the metastatic potential of multiple cancer types.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0359524"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389960","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":"The DnaJK chaperone of <i>Bacillus subtilis</i> post-transcriptionally regulates gene expression through the YlxR(RnpM)/RNase P complex.","authors":"Mitsuo Ogura, Yu Kanesaki, Hirofumi Yoshikawa, Koki Haga","doi":"10.1128/mbio.04053-24","DOIUrl":"10.1128/mbio.04053-24","url":null,"abstract":"<p><p>To survive in harsh natural environments, translation and mRNA metabolism must be tightly and coordinately controlled, as saving biological costs increases fitness. However, the roles of protein chaperones in this control system are unclear. This study proposes the novel aspect of the link between translation and mRNA metabolism, that is, the co-translational DnaJK chaperone activity is involved in changes in mRNA metabolism by RNase P. We found that the expression of <i>proBA,</i> which encodes proline biosynthetic enzymes, is regulated by <i>ylxR</i>(<i>rnpM</i>) through the <i>proBA</i> promoter. YlxR(RnpM), which is associated with RNase P, was also involved in the posttranscriptional regulation of <i>proBA</i>. To clarify this posttranscriptional regulation, we screened transposon (Tn)-inserted mutants for cells with low <i>proB::lacZ</i> expression and identified the DnaJK chaperone as a regulator of <i>proB</i>. To explore the possibility that the complex of YlxR(RnpM) and RNase P might work with DnaJK, we performed an epistatic analysis using the <i>lacZ</i> fusions, which revealed that the regulation of <i>proB</i> by DnaJK/YlxR(RnpM)/RNase P, that is, co-translational chaperone activity, controlled mRNA metabolism. RNA sequencing analysis of cells deficient in the RNA component of RNase P (<i>rnpB</i>) revealed that 261 genes were upregulated in the <i>rnpB</i>::Tn strain. Among them, we identified <i>yoyD/yodF, besA</i>, and <i>epeXE,</i> which were also under the control of DnaJK/YlxR(RnpM)/RNase P regulatory cascade. Finally, we performed yeast two-hybrid analysis using DnaK as bait and identified two genes, <i>spoIVCA</i> and <i>nupG</i>, whose expression was post-transcriptionally regulated by DnaJK but independent of YlxR(RnpM). These results suggest a broader role for posttranscriptional gene regulation by DnaJK.IMPORTANCE<i>Bacillus subtilis</i> lacking the DnaJK chaperone has not been reported to exhibit a distinct phenotype. However, our study revealed proline-dependent growth in a minimal medium in the <i>dnaJ</i>::Tn strain. Inhibition of <i>spoIVCA</i> expression in this strain was identified as a probable cause of the sporulation deficiency in previous and current studies using a single cell-level analysis. We also observed posttranscriptional regulation of <i>proBA</i> by the DnaJK and YlxR(RnpM)/RNase P complex. LacZ analyses of <i>proB::lacZ</i> in different backgrounds suggested that the above regulation ultimately functions in mRNA metabolism. In DnaJK-deficient cells, the nascent peptide may be misfolded, and if DnaJK chaperone activity is lost, such a signal may be transferred to RNase P. Therefore, <i>proBA</i> mRNA may be degraded in an RNase P-dependent manner if the misfolding of the polypeptide translated from this mRNA is detected. This system is useful for reducing the biological costs of futile mRNA elongation.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0405324"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390858","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":"The unique structure of the highly conserved PPLP region in HIV-1 Vif is critical for the formation of APOBEC3 recognition interfaces.","authors":"Yasumasa Iwatani, Kazuhiro Matsuoka, Hirotaka Ode, Mai Kubota, Yoshihiro Nakata, Yuka Setoyama, Kanako Kojima, Mayumi Imahashi, Yoshiyuki Yokomaku","doi":"10.1128/mbio.03332-24","DOIUrl":"10.1128/mbio.03332-24","url":null,"abstract":"<p><p>The human cellular cytidine deaminases APOBEC3s (A3s) inhibit virion infectivity factor (Vif)-deficient HIV-1 replication. However, virus-encoded Vifs abolish this defense system by specifically recruiting A3s to an E3 ubiquitin ligase complex to induce their degradation. The highly conserved Vif PPLP motif is critical for the Vif-mediated antagonism of A3s and is believed to be important for Vif multimerization. However, how the PPLP motif dictates the functions of Vif remains unclear. Here, we aimed to elucidate this mechanism using biochemical and structural biology approaches. First, we found that no stable Vif multimer complexes formed in our tandem coimmunoprecipitation assays. Next, a series of Vif truncation mutants were constructed, and the short α-helix α6 just downstream of PPLP was found to be the smallest fragment essential for efficient A3G degradation in cells. <i>In silico</i> structural analysis suggested that PPLP-α6 adopts a stable L-shaped conformation when complexed in Vif/CBF-β and contributes to the structural integrity of Vif. <i>In vitro</i> ubiquitination assays with recombinant proteins confirmed that PPLP-α6 is necessary to form the functional complex of the E3 ligase adaptor of Vif/CBF-β/elongin B/elongin C. Additionally, mutations of the highly conserved PPLP-α6 hydrophobic residues severely disrupted Vif function. In the Vif structure, PPLP-α6 is positioned behind α1-α2 that constitutes the A3-binding Vif interfaces. Therefore, both the PPLP motif and α6 play critical allosteric roles in maintaining the integrity of the A3 interaction interfaces. Our findings will also provide important data for the design of novel anti-HIV-1 compounds that disrupt the A3-binding Vif interfaces.IMPORTANCEThe APOBEC3 (A3) family enzymes potently block the replication of retroviruses, such as HIV-1. However, HIV-1 expresses Vif, a small multifaceted protein that binds and specifically eliminates A3s in infected cells via ubiquitination-proteasome degradation. Thus, A3-Vif interactions are attractive targets for anti-HIV-1 drug development. The Vif PPLP motif that is distal from these interfaces is necessary for A3 degradation; however, the mechanism by which PPLP participates in A3 degradation is unknown. In this study, we performed biochemical and structural biology analyses to elucidate the underlying mechanisms involved. We found that the PPLP motif, in addition to the short downstream fragment α6, forms a stable L-shaped conformation and acts as a scaffold for the A3 recognition interfaces. Importantly, mutations in α6 abolished Vif function to antagonize multiple A3 family enzymes. These findings provide important data for the development of novel HIV-1 inhibitors that utilize A3s as cellular defense enzymes.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0333224"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007883","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":"Interplay between the cyclophilin homology domain of RANBP2 and MX2 regulates HIV-1 capsid dependencies on nucleoporins.","authors":"Haley Flick, Ananya Venbakkam, Parmit K Singh, Bailey Layish, Szu-Wei Huang, Rajalingam Radhakrishnan, Mamuka Kvaratskhelia, Alan N Engelman, Melissa Kane","doi":"10.1128/mbio.02646-24","DOIUrl":"10.1128/mbio.02646-24","url":null,"abstract":"<p><p>Interlinked interactions between the viral capsid (CA), nucleoporins (Nups), and the antiviral protein myxovirus resistance 2 (MX2/MXB) influence human immunodeficiency virus 1 (HIV-1) nuclear entry and the outcome of infection. Although RANBP2/NUP358 has been repeatedly identified as a critical player in HIV-1 nuclear import and MX2 activity, the mechanism by which RANBP2 facilitates HIV-1 infection is not well understood. To explore the interactions between MX2, the viral CA, and RANBP2, we utilized CRISPR-Cas9 to generate cell lines expressing RANBP2 from its endogenous locus but lacking the C-terminal cyclophilin (Cyp) homology domain and found that both HIV-1 and HIV-2 infections were reduced significantly in RANBP2_ΔCyp cells. Importantly, although MX2 still localized to the nuclear pore complex in RANBP2_ΔCyp cells, antiviral activity against HIV-1 was decreased. By generating cells expressing specific point mutations in the RANBP2-Cyp domain, we determined that the effect of the RANBP2-Cyp domain on MX2 anti-HIV-1 activity is due to direct interactions between RANBP2 and CA. We further determined that CypA and RANBP2-Cyp have similar effects on HIV-1 integration targeting. Finally, we found that the Nup requirements for HIV infection and MX2 activity were altered in cells lacking the RANBP2-Cyp domain. These findings demonstrate that the RANBP2-Cyp domain affects viral infection and MX2 sensitivity by altering CA-specific interactions with cellular factors that affect nuclear import and integration targeting.</p><p><strong>Importance: </strong>Human immunodeficiency virus 1 (HIV-1) entry into the nucleus is an essential step in viral replication that involves complex interactions between the viral capsid (CA) and multiple cellular proteins, including nucleoporins (Nups) such as RANBP2. Nups also mediate the function of the antiviral protein myxovirus resistance 2 (MX2); however, determining the precise role of Nups in HIV infection has proved challenging due to the complex nature of the nuclear pore complex (NPC) and significant pleiotropic effects elicited by Nup depletion. We have used precise gene editing to assess the role of the cyclophilin domain of RANBP2 in HIV-1 infection and MX2 activity. We find that this domain affects viral infection, nucleoporin requirements, MX2 sensitivity, and integration targeting in a CA-specific manner, providing detailed insights into how RANBP2 contributes to HIV-1 infection.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0264624"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033427","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":"Evaluation of tumor-colonizing <i>Salmonella</i> strains using the chick chorioallantoic membrane model.","authors":"Khin K Z Mon, Linda J Kenney","doi":"10.1128/mbio.03590-24","DOIUrl":"10.1128/mbio.03590-24","url":null,"abstract":"<p><p>The chick embryo chorioallantoic membrane (CAM) tumor model is a valuable preclinical model for studying the tumor-colonizing process of <i>Salmonella enterica</i> serovar Typhimurium. It offers advantages such as cost-effectiveness, rapid turnaround, reduced engraftment issues, and ease of observation. In this study, we explored and validated the applicability of the partially immune-deficient CAM tumor model. Herein, we demonstrate that <i>Salmonella</i> preferentially colonizes tumors and directly causes tumor cell death. Bacterial migration, tumor colonization, and intra-tumor distribution did not require flagellar-mediated motility. The vast majority of <i>Salmonella</i> that colonized the CAM tumor were extracellular. Thus, tumor invasion was independent of both <i>Salmonella</i> pathogenicity island-1-encoded and <i>Salmonella</i> pathogenicity island-2-encoded type III secretion systems. Surprisingly, the extracellular residence of <i>Salmonella</i> on CAM tumors did not require biofilm formation. We evaluated our wild-type parental strain compared to the attenuated clinical strain VNP20009 and discovered a reduced tumor colonization capability of VNP20009. The inability to effectively colonize CAM tumors potentially explains the reduced anti-tumor efficacy of VNP20009. Our work establishes the xenograft CAM model as an informative and predictive screening platform for studying tumor-colonizing <i>Salmonella</i>.IMPORTANCECancer has a major impact on society, as it poses a significant health burden to human populations worldwide. <i>Salmonella</i> Typhimurium has demonstrated promise in cancer treatment by exerting direct tumoricidal effects and enhancing host-mediated anti-tumor immunity in xenograft mouse studies. A general understanding of its pathogenesis and the relative ease of genetic manipulation support the development of attenuated strains for therapeutic use. Alternative <i>in ovo</i> models, such as the chorioallantoic membrane tumor model, present a suitable screening platform to accelerate the development of therapeutic strains. It allows for rapid evaluation of <i>Salmonella</i> strains to assess their efficacy and potential as oncolytic agents. The present study establishes that the <i>in ovo</i> tumor model can be utilized as a preclinical tool for evaluating oncolytic <i>Salmonella</i>, bridging the gap between <i>in vitro</i> and <i>in vivo</i> screening.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0359024"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052973","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":"Erratum for Guo et al., \"Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis\".","authors":"Mingquan Guo, Guojun Wu, Yun Tan, Yan Li, Xin Jin, Weiqiang Qi, Xiaokui Guo, Chenhong Zhang, Zhaoqin Zhu, Liping Zhao","doi":"10.1128/mbio.00149-25","DOIUrl":"10.1128/mbio.00149-25","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0014925"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059499","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":"Cells that survive acute SARS-CoV-2 infection contribute to inflammation and lung regeneration in mice.","authors":"Ruangang Pan, David K Meyerholz, Stanley Perlman","doi":"10.1128/mbio.03693-24","DOIUrl":"10.1128/mbio.03693-24","url":null,"abstract":"<p><p>Post-acute sequelae of COVID-19 involves several organs, but its basis remains poorly understood. Some infected cells in mice survive the acute infection and persist for extended periods in the respiratory tract but not in other tissues. Here, we describe two experimental models of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection to assess the effect of viral virulence on previously infected cells. Both approaches use lineage tracking of previously infected cells. In mice infected with a highly pathogenic mouse-adapted SARS-CoV-2, alveolar type 2 cells (AT2) but not alveolar type 1 (AT1) cells survived the acute infection. These cells became activated, differentiated into an AT2-to-AT1 transitional cell state (KRT8⁺ pre-alveolar type 1 transitional cell state). Additionally, nearby uninfected AT2 cells upregulated the transitional marker KRT8, thereby contributing to lung regeneration. In mice sensitized to infection by transduction with Ad5-hACE2, the infection is nonlethal, and AT1 cells survived the infection. Consequently, recovery in these mice was more rapid. Taken together, these results provide an explanation for how SARS-CoV-2 virulence contributes to poor outcomes and affects clinical recovery and lung regeneration. We also identified a new mechanism by which SARS-CoV-2 impacts lung recovery, even at times when infectious virus cannot be detected.</p><p><strong>Importance: </strong>A major consequence of the COVID-19 pandemic is that many survivors have long-term sequelae, which are not well understood. These involve many organs, with the respiratory tract being a common site of long-term effects. Many of these sequelae can be found in mice infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this study, we have focused on the lungs, with particular interest in the fate and role of cells that were infected with SARS-CoV-2 and survived the acute infection. We found that some infected cells survive acute SARS-CoV-2 infection and that these surviving cells both contribute to the immune response in the lungs and are involved in lung recovery. These findings illustrate previously unexplored aspects of recovery from SARS-CoV-2 induced pneumonia and may be relevant for understanding aspects of post-acute sequelae of COVID-19.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0369324"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059561","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":"Structural mapping of polyclonal IgG responses to HA after influenza virus vaccination or infection.","authors":"André Nicolás León, Alesandra J Rodriguez, Sara T Richey, Alba Torrents de la Pena, Rachael M Wolters, Abigail M Jackson, Katherine Webb, C Buddy Creech, Sandra Yoder, Philip A Mudd, James E Crowe, Julianna Han, Andrew B Ward","doi":"10.1128/mbio.02030-24","DOIUrl":"10.1128/mbio.02030-24","url":null,"abstract":"<p><p>Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses against H1 predominantly targeted the central stem epitope in infected patients and vaccinated donors, whereas head epitopes were more prominently targeted on H3. Responses against H3 were less abundant, but a greater diversity of H3 epitopes were targeted relative to H1. While our analysis is limited by sample size, on average, vaccinated donors responded to a greater diversity of epitopes on both H1 and H3 than infected patients. These data establish a baseline for assessing polyclonal antibody responses in vaccination and infection, providing a context for future vaccine trials and emphasizing the need for further characterization of protective responses toward conserved epitopes. (201 words)IMPORTANCESeasonal influenza viruses cause hundreds of thousands of deaths each year and up to a billion infections; under the proper circumstances, influenza A viruses with pandemic potential could threaten the lives of millions more. The variable efficacies of traditional influenza virus vaccines and the desire to prevent pandemic influenzas have motivated work toward finding a universal flu vaccine. Many promising universal flu vaccine candidates currently focus on guiding immune responses to highly conserved epitopes on the central stem of the influenza hemagglutinin viral fusion protein. To support the further development of these stem-targeting vaccine candidates, in this study, we use negative stain electron microscopy to assess the prevalence of central stem-targeting antibodies in individuals who were exposed to influenza antigens through traditional vaccination and/or natural infection during the 2018-2019 flu season.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0203024"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255932","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":"mGem: The complexity of viral entry-one virus, many receptors.","authors":"Terence S Dermody, Danica M Sutherland","doi":"10.1128/mbio.02964-24","DOIUrl":"10.1128/mbio.02964-24","url":null,"abstract":"<p><p>Binding to cellular receptors initiates viral replication and dictates sites in the host infected by the virus. As illustrated by mammalian orthoreovirus (reovirus), viruses can bind several types of receptors using distinct capsid components to facilitate the viral entry steps of attachment, internalization, and disassembly. The outer of the two concentric capsids of reovirus virions is formed by four viral proteins, three of which bind receptors. These capsid-receptor interactions mediate stepwise entry of reovirus, dictate viral tropism in infected animals, and expand the viral host range. Engagement of independent receptors by different capsid proteins is a property of many pathogenic viruses and illustrates common themes of receptor use in viral entry and disease.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0296424"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390367","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}