Frontiers in Cellular and Infection Microbiology最新文献

{"title":"Efficacy and safety of different drugs for the treatment of bacterial vaginosis: a systematic review and network meta-analysis.","authors":"Yuxin Fan, Yanhong Gu, Yi Xian, Qinya Li, Youli He, Kaiyang Chen, Hui Yu, Huan Deng, Li Xiong, Zhiwei Cui, Yang Yang, Yin Xiang","doi":"10.3389/fcimb.2024.1402346","DOIUrl":"10.3389/fcimb.2024.1402346","url":null,"abstract":"<p><strong>Objective: </strong>Bacterial vaginosis is a disease caused by vaginal microecology disorder, which seriously affects female health. At present, there are many drugs to treat BV, and this study aims to compare the efficacy and safety of multiple drugs for BV through a network meta-analysis (NMA).</p><p><strong>Methods: </strong>All studies were sourced from PubMed and Embase databases from the establishment date to April 13, 2023. We evaluated the clinical cure success rate and adverse effects (abnormal increase in vaginal discharge, external genital irritation, and vulvar itching) and performed subgroup analyses of the clinical cure success rate for different modes of administration. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis.</p><p><strong>Results: </strong>We included 42 studies that met the criteria, involving a total of 8382 patients. Network meta-analysis results showed that metronidazole and secnidazole had a higher rate of adverse reactions than placebo (RR 7.06; 95%-CI 2.61-19.10, RR 4.03; 95%-CI 1.63-9.98), the adverse reaction rate of probiotics group was lower than that of metronidazole group (RR 0.44; 95%-CI 0.21-0.93). The clinical cure rate of oral ornidazole was better than clindamycin (RR 16.08; 95%-CI 1.72-150.47), Secnidazole (RR 8.17; 95%-CI 1.66-40.25) and probiotics. Direct meta-analysis results showed that ornidazole had a better clinical cure rate than Secnidazole (RR 1.22; 95%-CI 1.10-1.34), oral ornidazole had a better clinical cure rate than Secnidazole (RR 1.23; 95%-CI 1.11-1.36). The clinical cure rate of vaginal application of sucrose was better than metronidazole (RR 1.12; 95%-CI 1.03-1.21) and metronidazole had a lower clinical cure rate than probiotics (RR 0.68; 95%-CI 0.52-0.88).</p><p><strong>Conclusions: </strong>The results of this systematic review and network meta-analysis suggest that ornidazole may be an effective alternative for the treatment of BV, and that sucrose and probiotics are potential BV treatments that need to be validated by more high-quality clinical studies in the future.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Fusobacterium nucleatum</i> elicits subspecies-specific responses in human neutrophils.","authors":"Maria Muchova, Sarah A Kuehne, Melissa M Grant, Peter P Smith, Malee Nagi, Iain L C Chapple, Josefine Hirschfeld","doi":"10.3389/fcimb.2024.1449539","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1449539","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum</i> as a Gram-negative anaerobe plays a key bridging role in oral biofilms. It is involved in periodontal and extraoral diseases, the most prominent being colorectal cancer. Five subspecies are recognised: <i>animalis, fusiforme, nucleatum, polymorphum</i> and <i>vincentii</i>. Subspecies interact with neutrophils constantly patrolling tissues to remove microbial intruders. Neutrophil antimicrobial activities include generation of reactive oxygen species (ROS), formation of neutrophil extracellular traps (NETs) and release of cytokines and neutrophil enzymes. Subspecies-specific differences in immunogenicity have previously been observed in a neutrophil-like cell line but were not investigated in human neutrophils. Additionally, neutrophil responses to planktonic and biofilm-grown <i>F. nucleatum</i> have not been studied to date. The aims of this study were to compare the immunogenicity of planktonic and biofilm-grown <i>F. nucleatum</i> and to investigate potential differences in human neutrophil responses when stimulated with individual <i>F. nucleatum</i> subspecies. Human neutrophils isolated from peripheral blood were stimulated with planktonic and biofilm-grown <i>F. nucleatum</i> subspecies. Generation of ROS and NET formation were quantified by luminescence and fluorescence assays, respectively. Secretion of cytokines (IL-1β, TNF-α, IL-6, IL-8), neutrophil elastase and matrix metalloproteinase-9 was quantified by enzyme-linked immunosorbent assay (ELISA). Neutrophil responses showed biofilm-grown bacteria induced a significantly higher total and intracellular ROS response, as well as shorter time to total ROS release. Biofilm-grown <i>F. nucleatum</i> led to significantly lower IL-1β release. We found significant differences among individual subspecies in terms of total, intracellular ROS and extracellular superoxide. Subspecies <i>polymorphum</i> stimulated the highest mean amount of NET release. Amounts of cytokines released differed significantly among subspecies, while no differences were found in lysosomal enzyme release. Immunogenicity of <i>F. nucleatum</i> in human neutrophils is highly subspecies-specific <i>in vitro</i> with regard to ROS release and cytokine production. Understanding subspecies-specific immunogenicity of <i>F. nucleatum</i> may facilitate the discovery of novel therapeutic targets in <i>F. nucleatum</i>-mediated diseases.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duplex recombinase aided amplification-lateral flow dipstick assay for rapid distinction of <i>Mycobacterium tuberculosis</i> and <i>Mycobacterium avium complex</i>.","authors":"Ke Chen, Junze Zhang, Simeng Wang, Zhengjun Yi, Yurong Fu","doi":"10.3389/fcimb.2024.1454096","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1454096","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to develop a novel diagnostic approach using the recombinase aided amplification-lateral flow dipstick(RAA-LFD) assay for the distinction of <i>Mycobacterium tuberculosis</i> (MTB) and <i>Mycobacterium avium complex</i> (MAC), enabling rapid and convenient as well as accurate identification of them in clinical samples.</p><p><strong>Methods: </strong>Our study established a duplex RAA-LFD assay capable of discriminating between MTB and MAC. Based on the principles of RAA primer and probe design, specific primers and probes were developed targeting the MTB <i>IS6110</i> and the MAC <i>DT1</i> separately. Optimization of reaction time points and temperatures was conducted, followed by an evaluation of specificity, sensitivity, and reproducibility. The established detection method was then applied to clinical samples and compared with smear microscopy, liquid culture, LAMP, and Xpert/MTB RIF in terms of diagnostic performance.</p><p><strong>Results: </strong>The complete workflow allows for the effective amplification of the MTB <i>IS6110</i> and MAC <i>DT1</i> target sequences at constant 37°C within 20min, and the amplification products can be visually observed on the LFD test strip. This method exhibits high specificity, showing no cross-reactivity with nucleic acids from <i>M. kansassi</i>, <i>M. abscessus, M. gordonae, M. chelonae, M. fortuitum, M. scrofulaceum, M. malmoense, M. chimaera, M. szulgai</i> and common respiratory pathogens. It also demonstrates high sensitivity, with a detection limit as low as 10² CFU/mL. Additionally, the method's Coefficient of Variation (CV) is less than 5%, ensuring excellent repeatability and reliability. Furthermore, clinical performance evaluations, using Xpert/MTB RIF as the gold standard, demonstrated that the duplex RAA-LFD assay achieves a sensitivity of 92.86% and a specificity of 93.75%. It is also noteworthy that the assay exhibits considerable diagnostic efficacy in smear-negative patients.</p><p><strong>Conclusions: </strong>Our study introduces a rapid, specific, and sensitive duplex RAA-LFD assay for the discriminatory diagnosis of MTB and MAC. This method represents a significant advancement in the field of infectious disease diagnostics, offering a valuable tool for rapid detection and management of MTB and MAC infections. The implementation of this approach in point-of-care settings could greatly enhance TB control and prevention efforts, especially in resource-limited environments.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of the vaginal microbiota and vaginal metabolites in women with cervical dysplasia.","authors":"Tiantian Yu, Shan Gao, Fen Jin, Bingbing Yan, Wendong Wang, Zhongmin Wang","doi":"10.3389/fcimb.2024.1457216","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1457216","url":null,"abstract":"<p><strong>Introduction: </strong>Emerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia.</p><p><strong>Methods: </strong>In this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics, and integrated analysis.</p><p><strong>Results: </strong>The results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, <i>Lactobacillus</i> was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased <i>Lactobacillus</i> abundance and CC group-decreased metabolites. <i>Lactobacillus iners</i> was both negative to <i>nadB</i> and <i>kynU</i> genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer.</p><p><strong>Discussion: </strong>Our results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Antiviral monoclonal antibody therapies.","authors":"Catalina Florez, Denise Haslwanter, Rohit K Jangra","doi":"10.3389/fcimb.2024.1484448","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1484448","url":null,"abstract":"","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metalloprotease secreted by an environmentally acquired gut bacterium hinders <i>Borrelia afzelii</i> colonization in <i>Ixodes ricinus</i>.","authors":"Adnan Hodžić, Gorana Veinović, Amer Alić, David Seki, Martin Kunert, Georgi Nikolov, Ratko Sukara, Jovana Šupić, Snežana Tomanović, David Berry","doi":"10.3389/fcimb.2024.1476266","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1476266","url":null,"abstract":"<p><p>Although the importance of the microbiome in the context of tick biology and vector competence has recently come into a broader research focus, the field is still in its infancy and the complex ecological interactions between the tick residential bacteria and pathogens are obscure. Here, we show that an environmentally acquired gut bacterium has the potential to impair <i>Borrelia afzelii</i> colonization within the tick vector through a secreted metalloprotease. Oral introduction of either <i>Bacillus cereus</i> LTG-1 isolate or its purified enhancin (<i>Bc</i>Enhancin) protein significantly reduces <i>B. afzelii</i> burden in the guts of <i>Ixodes ricinus</i> ticks. This effect is attributed to the ability of <i>Bc</i>Enhancin to degrade a glycan-rich peritrophic matrix (PM), which is a gut protective barrier essential for <i>Borrelia</i> survival. Our study highlights the importance of the gut microbiome in determining tick vector competence and provides a deeper mechanistic insight into the complex network of interactions between <i>Borrelia</i>, the tick, and the tick microbiome.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of porcine PARP11 as a restricted factor for pseudorabies virus.","authors":"Chunyun Qi, Dehua Zhao, Xi Wang, Lanxin Hu, Yao Wang, Heyong Wu, Feng Li, Jian Zhou, Tianyi Zhang, Aosi Qi, Yuran Huo, Qiuse Tu, Shuyu Zhong, Hongming Yuan, Dongmei Lv, Shouqing Yan, Hongsheng Ouyang, Daxin Pang, Zicong Xie","doi":"10.3389/fcimb.2024.1414827","DOIUrl":"10.3389/fcimb.2024.1414827","url":null,"abstract":"<p><strong>Introduction: </strong>PRV infection in swine can cause devastating disease and pose a potential threat to humans. Advancing the interplay between PRV and host is essential to elucidate the pathogenic mechanism of PRV and identify novel anti-PRV targets.</p><p><strong>Methods: </strong>PARP11-KO PK-15 cells were firstly constructed by CRISPR/Cas9 technology. Next, the effect of PARP11-KO on PRV infection was determined by RT-qPCR, TCID50 assay, RNA-seq, and western blot.</p><p><strong>Results and discussion: </strong>In this study, we identified PARP11 as a host factor that can significantly affect PRV infection. Inhibition of PARP11 and knockout of PARP11 can significantly promoted PRV infection. Subsequently, we further found that PARP11 knockout upregulated the transcription of NXF1 and CRM1, resulting in enhanced transcription of viral genes. Furthermore, we also found that PARP11 knockout could activate the autophagy pathway and suppress the mTOR pathway during PRV infection. These findings could provide insight into the mechanism in which PARP11 participated during PRV infection and offer a potential target to develop anti-PRV therapies.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage variants in laboratory research: most are well done, but some are RAW.","authors":"Marc Herb, Valentin Schatz, Karina Hadrian, Deniz Hos, Bohdan Holoborodko, Jonathan Jantsch, Natascha Brigo","doi":"10.3389/fcimb.2024.1457323","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1457323","url":null,"abstract":"<p><p>Macrophages play a pivotal role in the innate immune response. While their most characteristic function is phagocytosis, it is important not to solely characterize macrophages by this activity. Their crucial roles in body development, homeostasis, repair, and immune responses against pathogens necessitate a broader understanding. Macrophages exhibit remarkable plasticity, allowing them to modify their functional characteristics in response to the tissue microenvironment (tissue type, presence of pathogens or inflammation, and specific signals from neighboring cells) swiftly. While there is no single defined \"macrophage\" entity, there is a diverse array of macrophage types because macrophage ontogeny involves the differentiation of progenitor cells into tissue-resident macrophages, as well as the recruitment and differentiation of circulating monocytes in response to tissue-specific cues. In addition, macrophages continuously sense and respond to environmental cues and tissue conditions, adjusting their functional and metabolic states accordingly. Consequently, it is of paramount importance to comprehend the heterogeneous origins and functions of macrophages employed in <i>in vitro</i> studies, as each available <i>in vitro</i> macrophage model is associated with specific sets of strengths and limitations. This review centers its attention on a comprehensive comparison between immortalized mouse macrophage cell lines and primary mouse macrophages. It provides a detailed analysis of the strengths and weaknesses inherent in these <i>in vitro</i> models. Finally, it explores the subtle distinctions between diverse macrophage cell lines, offering insights into numerous factors beyond the model type that can profoundly influence macrophage function.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of effusion adenosine deaminase, γ-interferon release assay and effusion lactatedehy drogenase/effusion adenosine deaminase for tuberculous pleural effusion in patients aged 60 years and above.","authors":"Fei Guo, Chen Huimin, Wei Xia, Yilin Xu, Weijiang Jin, Fang Liu","doi":"10.3389/fcimb.2024.1444238","DOIUrl":"10.3389/fcimb.2024.1444238","url":null,"abstract":"<p><strong>Background: </strong>China is experiencing rapid growth in its population of older adults, which may lead to increased susceptibility to tuberculous pleural effusion (TPE) due to age-related changes in the immune system. This study aimed to investigate the diagnostic potential of multiple biomarkers in individuals aged 60 years and above with pleural effusion.</p><p><strong>Methods: </strong>A total of 519 adult patients from Ningbo First Hospital were included in the study, with 7 biomarkers and their ratios in serum and pleural effusion analyzed using logistic regression analysis. Effusion Adenosine Deaminase(ADA), γ-Interferon Release Assay(IGRA), and Effusion lactatedehy drogenase(LDH)/Effusion ADA were identified as valuable parameters for differentiating TPE from non-TPE, particularly in individuals aged 60 years and older.</p><p><strong>Results: </strong>Effusion ADA, IGRA, and Effusion LDH/Effusion ADA were identified as valuable parameters for the differential diagnosis of TPE from non-TPE, showing good diagnostic performance in individuals aged 60 years and older. The combined diagnosis of these three indexes achieved the highest diagnostic accuracy for TPE in this age group, with an AUC of 0.925, sensitivity of 85.23%, and specificity of 89.57%.</p><p><strong>Conclusions: </strong>Overall, the study highlights the importance of using multiple indicators for a combined diagnosis to improve diagnostic efficacy in detecting tuberculous pleurisy in older individuals as for young patients.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-dependent C-to-U RNA editing in SARS-CoV-2 creates novel viral genes with optimized expressibility.","authors":"Pirun Zhang, Wenli Zhang, Jiahuan Li, Huiying Liu, Yantong Yu, Xiaoping Yang, Wenqing Jiang","doi":"10.3389/fcimb.2024.1476605","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1476605","url":null,"abstract":"<p><p>Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the \"AUG-gain mutations\" caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (<i>d</i>AF/<i>d</i>t) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of <i>de novo</i> genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}