Emerging Microbes & Infections最新文献

{"title":"A surrogate BSL2-compliant infection model recapitulating key aspects of human Marburg virus disease.","authors":"Wanying Yang, Wujie Zhou, Bo Liang, Xiaojun Hu, Shen Wang, Zhenshan Wang, Tiecheng Wang, Xianzhu Xia, Na Feng, Yongkun Zhao, Feihu Yan","doi":"10.1080/22221751.2024.2449083","DOIUrl":"10.1080/22221751.2024.2449083","url":null,"abstract":"<p><p>Marburg virus disease (MVD) is a severe infectious disease caused by the Marburg virus (MARV), posing a significant threat to humans. MARV needs to be operated under strict biosafety Level 4 (BSL-4) laboratory conditions. Therefore, accessible and practical animal models are urgently needed to advance prophylactic and therapeutic strategies for MARV. In this study, we constructed a recombinant vesicular stomatitis virus (VSV) expressing the Marburg virus glycoprotein (VSV-MARV/GP). Syrian hamsters infected with VSV-MARV/GP presented symptoms such as thrombocytopenia, lymphopenia, haemophilia, and multiorgan failure, developing a severe systemic disease akin to that observed in human MARV patients. Notably, the pathogenicity was found to be species-specific, age-related, sex-associated, and challenge route-dependent. Subsequently, the therapeutic efficacy of the MR191 monoclonal antibody was validated in this model. In summary, this alternative model is an effective tool for rapidly screening medical countermeasures against MARV GP in vivo under BSL-2 conditions.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2449083"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914040","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":"An immunocompetent mouse model revealed that congenital Zika virus infection disrupted hippocampal function by activating autophagy.","authors":"Wei Yang, Zhan-Zhan Bian, Zhe Li, Yi-Teng Zhang, Li-Bo Liu, Jia-Tong Chang, Dan Li, Pei-Gang Wang, Jing An, Wei Wang","doi":"10.1080/22221751.2025.2465327","DOIUrl":"10.1080/22221751.2025.2465327","url":null,"abstract":"<p><p>Congenital Zika virus (ZIKV) infection significantly affects neurological development in infants and subsequently induces neurodevelopmental abnormality symptoms; however, the potential mechanism is still unknown. Therefore, in order to effectively intervene in neurodevelopmental abnormalities in infected infants, it is necessary to identify the main brain regions affected by congenital infection. In this study, we constructed a congenital ZIKV-infected murine model using immunocompetent human STAT2 knock-in mice, which presented long-term neurodevelopmental abnormalities with abnormal neurodevelopmental symptoms. We found that the hippocampus, which regulates cognitive behaviour and processes spatial information and navigation, was the main brain region affected by congenital infection and that hippocampal cells were more prone to autophagy during the growth period of these mice at the transcriptional and pathological levels. These findings highlighted that congenital ZIKV infection could interrupt hippocampal function by activating autophagy, thus providing a theoretical basis for the clinical treatment of congenital ZIKV-infected infants.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2465327"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406511","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":"Reverse genetics-derived cattle H5N1 virus from Clade 2.3.4.4b shows enhanced systemic infectivity and pathogenicity than an older Clade 1 H5N1 virus in BALB/c mice.","authors":"Na Xiao, Xiang Yong Oong, Yanxia Chen, Can Li, Howard Chun-Ho Chung, Pui Wang, Zhanhong Ye, Alvin Hiu-Chung Lam, Jianpiao Cai, Wenchen Song, Andrew Chak-Yiu Lee, Hin Chu, Kin-Hang Kok, Jasper Fuk-Woo Chan, Shuofeng Yuan, Honglin Chen, Kwok-Yung Yuen, Anna Jin-Xia Zhang","doi":"10.1080/22221751.2025.2475836","DOIUrl":"10.1080/22221751.2025.2475836","url":null,"abstract":"<p><p>The newly emerged avian influenza A H5N1 Clade 2.3.4.4b can infect dairy cows and shed live virus in their milk. Sporadic cattle-to-human infections have been reported, highlighting the urgent need to understand its pathogenesis in mammals. Using both non-lactating and lactating BALB/c mice, we examined the viral tissue tropism, histopathological damages, and host immune responses upon intranasal inoculation with a reverse-genetic virus constructed based on A/dairy cattle/Texas/24-008749-003/2024 (Cattle-H5N1) and comparing with an older reference Clade 1 virus, A/Vietnam/1194/2004 virus (VNM1194-H5N1). Cattle-H5N1 was highly lethal in mice (mLD₅₀ = 1.48PFU) with broad tissue tropism and produced higher titer in respiratory tissue and multiple extrapulmonary organs than VNM1194-H5N1. In the lungs, Cattle-H5N1 infection of airway epithelium, type II pneumocytes and CD45⁺ immune cells were at a higher frequency than those of VNM1194-H5N1-infected mice, resulting in severe epithelial destruction and diffuse alveolar damage accompanied by elevated lung and serum pro-inflammatory cytokine/chemokines. Although both H5N1 viruses showed lactating mammary gland tropism, the gland tissue was more severely damaged after Cattle-H5N1 infection with abundant viral antigens expression in glandular cells, associated fat and lymphoid tissues. Furthermore, more suckling mice co-housed with Cattle-H5N1 infected lactating mice were virus-positive (7/30 pups) than VNM1194-H5N1. Brains were heavily infected by Cattle-H5N1, and neurological signs such as body-rolling/spinning, trembling and/or limb paralysis were seen only in Cattle-H5N1 infected mice. The spleen was more severely damaged by Cattle-H5N1 infection, which showed massive viral antigen expression accompanied by severe apoptosis and splenic atrophy, concluding that Cattle-H5N1 is more virulent in mice than VNM1194-H5N1.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2475836"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540596","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":"Novel human coronavirus in an infant patient with pneumonia, Republic of Korea.","authors":"Kyungmin Park, Minsoo Shin, Augustine Natasha, Jongwoo Kim, Juyoung Noh, Seong-Gyu Kim, Bohyeon Kim, Jieun Park, Ye-Rin Seo, Hee-Kyung Cho, Kwan Soo Byun, Ji Hoon Kim, Young-Sun Lee, Jung Ok Shim, Won-Keun Kim, Jin-Won Song","doi":"10.1080/22221751.2025.2466705","DOIUrl":"10.1080/22221751.2025.2466705","url":null,"abstract":"<p><p>Coronaviruses (CoVs) pose a significant threat to public health, causing a wide spectrum of clinical manifestations and outcomes. Beyond precipitating global outbreaks, Human CoVs (HCoVs) are frequently found among patients with respiratory infections. To date, limited attention has been directed towards alphacoronaviruses due to their low prevalence and fatality rates. Nasal swab and serum samples were collected from a paediatric patient, and an epidemiological survey was conducted. Retrospective surveillance investigated the molecular prevalence of CoV in 880 rodents collected in the Republic of Korea (ROK) from 2018 to 2022. Next-generation sequencing (NGS) and phylogenetic analyses characterized the novel HCoV and closely related CoVs harboured by <i>Apodemus</i> spp. On 15 December 2022, a 103-day-old infant was admitted with fever, cough, sputum production, and rhinorrhea, diagnosed with human parainfluenza virus 1 (HPIV-1) and rhinovirus co-infection. Elevated AST/ALT levels indicated transient liver dysfunction on the fourth day of hospitalization. Metagenomic NGS (mNGS) identified a novel HCoV in nasal swab and serum samples. Retrospective rodent surveillance and phylogenetic analyses showed the novel HCoV was closely related to alphacoronaviruses carried by <i>Apodemus</i> spp. in the ROK and China. This case highlights the potential of mNGS to identify emerging pathogens and raises awareness of possible extra-respiratory manifestations, such as transient liver dysfunction, associated with novel HCoVs. While the liver injury in this case may be attributable to the novel HCoV, further research is necessary to elucidate its clinical significance, epidemiological prevalence, and zoonotic origins.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2466705"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406483","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":"An IS element-driven antisense RNA attenuates the expression of serotype 2 fimbriae and the cytotoxicity of <i>Bordetella pertussis</i>.","authors":"Alexandre D'Halluin, Denisa Petráčková, Ivana Čurnová, Jakub Držmíšek, Jan Čapek, Peggy Bouquet, Loïc Henin, Rudy Antoine, Loïc Coutte, Camille Locht, Branislav Večerek, David Hot","doi":"10.1080/22221751.2025.2451718","DOIUrl":"10.1080/22221751.2025.2451718","url":null,"abstract":"<p><p>Insertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In <i>Bordetella pertussis</i>, the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements and contribute to the diversity of the global <i>B. pertussis</i> population. Previously, we have shown that the majority of IS-specific endogenous promoters induce the synthesis of alternative transcripts and thereby affect the transcriptional landscape of <i>B. pertussis</i>. Here, we describe the regulatory RNA Rfi2, which is transcribed from the P_out promoter of the IS<i>481</i> gene <i>BP1118</i> antisense to the adjacent <i>fim2</i> gene encoding the major serotype 2 fimbrial subunit of <i>B. pertussis</i>. Among the classical bordetellae, Rfi2 is unique to <i>B. pertussis</i>, suggesting its specific role in virulence. We show that Rfi2 RNA attenuates <i>fim2</i> transcription and, consequently, the production of the Fim2 protein. Interestingly, the mutant that does not produce Rfi2 displayed significantly increased cytotoxicity towards human macrophages compared to the parental strain. This observation suggests that the Rfi2-mediated reduction in cytotoxicity represents an evolutionary adaptation of <i>B. pertussis</i> that fine-tunes its interaction with the human host. Given the immunogenicity of Fim2, we further hypothesize that Rfi2-mediated modulation of Fim2 production contributes to immune evasion. To our knowledge, Rfi2 represents the first functionally characterized IS element-driven antisense RNA that modulates the expression of a virulence gene.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2451718"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946573","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 polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials.","authors":"Zoe Moodie, Shuying Sue Li, Elena E Giorgi, LaTonya D Williams, One Dintwe, Lindsay N Carpp, Shiyu Chen, Kelly E Seaton, Sheetal S Sawant, Lu Zhang, Jack Heptinstall, Shuying Liu, Nicole Grunenberg, Frank Tomaka, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Julie A Ake, Sandhya Vasan, Giuseppe Pantaleo, Ian Frank, Lindsey R Baden, Paul A Goepfert, Michael Keefer, Mike Chirenje, Mina C Hosseinipour, Kathryn Mngadi, Fatima Laher, Nigel Garrett, Linda-Gail Bekker, Stephen De Rosa, Erica Andersen-Nissen, James G Kublin, Shan Lu, Peter B Gilbert, Glenda E Gray, Lawrence Corey, M Juliana McElrath, Georgia D Tomaras","doi":"10.1080/22221751.2025.2485317","DOIUrl":"10.1080/22221751.2025.2485317","url":null,"abstract":"<p><p>Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints - providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses - two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines.<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT01799954..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02109354..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02404311..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02207920..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02296541..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03284710..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02915016..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02997969..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03122223..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03409276..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02968849..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT03060629..<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT00223080..</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"14 1","pages":"2485317"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794947","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":"Marked neurotropism and potential adaptation of H5N1 clade 2.3.4.4.b virus in naturally infected domestic cats.","authors":"Shubhada K Chothe, Surabhi Srinivas, Sougat Misra, Noel Chandan Nallipogu, Elizabeth Gilbride, Lindsey LaBella, Swastidipa Mukherjee, Christian H Gauthier, Heidi L Pecoraro, Brett T Webb, James M Pipas, Santhamani Ramasamy, Suresh V Kuchipudi","doi":"10.1080/22221751.2024.2440498","DOIUrl":"10.1080/22221751.2024.2440498","url":null,"abstract":"<p><p>In April 2024, ten cats died in a rural South Dakota (SD) residence, showing respiratory and neurological symptoms. Necropsy and laboratory testing of two cats confirmed H5N1 clade 2.3.4.4b infection. The viral genome sequences are closely related to recent SD cattle H5N1 sequences. Cat H5N1 genomes had unique mutations, including T143A in haemagglutinin, known to affect infectivity and immune evasion, and two novel mutations in PA protein (F314L, L342Q) that may affect polymerase activity and virulence, suggesting potential virus adaptation. Dead cats showed systemic infection with lesions and viral antigens in multiple organs. Higher viral RNA and antigen in the brain indicated pronounced neurotropism. Lectin-histochemistry revealed widespread co-expression of sialic acid α-2,6 and α-2,3 receptors, suggesting cats could serve as mixing vessels for reassortment of avian and mammalian influenza viruses. No differences in clade 2.2 or 2.3.4.4b H5 pseudoviruses binding to cat lung/brain tissues indicated the neurotropism is unlikely mediated by receptor binding affinity.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2440498"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794621","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":"Mosquito populations originating from nonendemic areas have the potential to transmit recently emerging Japanese encephalitis virus genotype IV.","authors":"Astri Nur Faizah, Daisuke Kobayashi, Faustus Akankperiwen Azerigyik, Ryo Matsumura, Izumi Kai, Yoshihide Maekawa, Yukiko Higa, Kentaro Itokawa, Toshinori Sasaki, Kris Cahyo Mulyatno, Sri Subekti, Maria Inge Lusida, Etik Ainun Rohmah, Yasuko Mori, Yusuf Ozbel, Chizu Sanjoba, Tran Vu Phong, Tran Cong Tu, Shinji Kasai, Kyoko Sawabe, Haruhiko Isawa","doi":"10.1080/22221751.2024.2438661","DOIUrl":"10.1080/22221751.2024.2438661","url":null,"abstract":"<p><p>Japanese encephalitis virus (JEV) genotype IV (GIV) is one of the least common and most neglected genotypes worldwide, having been identified only on a few Indonesian islands until it was recently found to be the cause of outbreaks that occurred in several Australian states in early 2022. Given the limited availability of information, the vector range for JEV GIV remains unknown; thus, understanding this range could prove invaluable for future prevention efforts in new areas. Herein, we experimentally exposed four mosquito colonies originated from various countries with no previous reports of GIV to JEV GIV strain 19CxBa-83-Cv, which was isolated from <i>Culex vishnui</i> Theobald collected in Bali in 2019. At 7 and 14 days post-JEV GIV exposure through a membrane feeding method, mosquito bodies, head-wings-legs, and saliva were harvested for infection, dissemination, and transmission efficiency analyses. The results showed robust transmission efficiencies of the virus by <i>Culex tritaeniorhynchu</i>s Giles (∼74%) and <i>Aedes albopictus</i> Skuse (∼52%) from Japan, followed by <i>Culex quinquefasciatus</i> Say from Vietnam (∼35%) and <i>Culex pipiens</i> form <i>molestus</i> from Turkey (∼18%). Although significant differences were observed, we found that the four mosquito species could transmit JEV GIV. The efficiency of biological transmission of this restricted genotype by mosquitoes from various origins suggests that these mosquito species could support localized transmission if the genotype were introduced to their respective areas. This study emphasizes the importance of remaining vigilant and continuing arbovirus surveillance in all locations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2438661"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signalling pathway to facilitate viral replication.","authors":"Shixiong Zhou, Xianfeng Hui, Weiwei Wang, Chunbei Zhao, Meilin Jin, Yali Qin, Mingzhou Chen","doi":"10.1080/22221751.2024.2447620","DOIUrl":"10.1080/22221751.2024.2447620","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic RNA and is also present in various viral RNAs, where it plays a crucial role in regulating the viral life cycle. However, the molecular mechanisms through which viruses regulate host RNA m6A methylation are not fully understood. In this study, we reveal that SARS-CoV-2 and HCoV-OC43 infection enhance host m6A modification by activating the mTORC1 signalling pathway. Specifically, the viral non-structural protein nsp14 upregulates the expression of S-adenosylmethionine synthase MAT2A in an mTORC1-dependent manner. This mTORC1-MAT2A axis subsequently stimulates the synthesis of S-adenosylmethionine (SAM). The increase of SAM then enhances the m6A methylation of host RNA and facilitates viral replication. Our findings uncover a molecular mechanism by which viruses regulate host m6A methylation and provide insights into how SARS-CoV-2 hijacks host cellular epitranscriptomic modifications to promote its replication.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2447620"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913112","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":"Enhanced antibody response to the conformational non-RBD region <i>via</i> DNA prime-protein boost elicits broad cross-neutralization against SARS-CoV-2 variants.","authors":"Yun-Fei Ma, Kun Chen, Bowen Xie, Jiayi Zhu, Xuan He, Chunying Chen, Yuhe Renee Yang, Ye Liu","doi":"10.1080/22221751.2024.2447615","DOIUrl":"10.1080/22221751.2024.2447615","url":null,"abstract":"<p><p>Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants. <i>Via</i> analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2447615"},"PeriodicalIF":8.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892999","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}